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BSACI Rhinitis Guideline Scadding et al. 2015

BSACI guideline for the diagnosis and management of allergic and

non-allergic rhinitis (Revised Edition 2014; First edition 2007)

Glenis. K. Scadding*, Harsha Kariyawasamǂ, Guy Scadding‡, Rita Mirakian*, Roger J.

Buckleyɸ, Tina Dixon¥, Stephen R. Durham‡, Sophie Farooqueǂ, Pia AJ Huber, Nicholas

Jones¶, Susan Leech, Shuaib M. Nasser#, Richard Powell, Graham Roberts||, Guiseppina

Rotiroti*, Angela Simpson≠, Helen Smith§, Andy T. Clark#

*The Royal National Throat Nose and Ear Hospital, Gray’s Inn Road, London UK#Cambridge University Hospital NHS Foundation Trust, Cambridge UK‡Department of Upper Respiratory Medicine, Imperial College NHLI, Guy Scadding Building Royal Brompton

Campus, London UK≠Academic Division of Medicine and Surgery, Manchester University, Manchester UKǂChest and Allergy Department, St Mary’s Hospital, Imperial College NHS Trust, London UK¥Royal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool UK

¶The Park Hospital, Nottingham UK§Division of primary care and public health, University of Brighton, Brighton UK||Department of Child Health, University of Southampton Hospital, Southampton UKDepartment of Child Health, King’s College Hospital, London UKDepartment of Clinical Immunology and Allergy, Nottingham University, Nottingham UKɸVision and Eye Research Unit, Anglia Ruskin University, East Road, Cambridge, UKBritish Society for Allergy & Clinical Immunology, London, UK

Address for Correspondence:

Dr AT Clark

Cambridge University Hospitals NHS Foundation Trust

Box 40

Allergy Clinic

Cambridge CB2 0QQ

Email: [email protected]

Tel: 01223 762603

Keywords: allergic, allergen, allergy, antihistamine, anti-leukotriene, aspirin, asthma, BSACI,

quality of life, cat allergen, child, corticosteroid, cromoglicate, decongestant, guideline,

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house dust mite, idiopathic rhinitis, IgE, immunotherapy, ipratropium bromide, lactation,

nitric oxide, non-allergic, non-allergic, non- infectious rhinitis, NINAR, occupational,

pregnancy, rhinitis, rhinitis control, skin prick test, SOCC, subcutaneous immunotherapy,

sublingual immunotherapy, surgery

INTRODUCTION

Allergic rhinoconjunctivitis (AR) remains the most common immunological disease in man

and is still subject to under-recognition and poor management (1NEW). This matters

because AR significantly reduces quality of life (QOL) (Laforest and others 2005), interferes

with both attendance and performance at school and work (Blaiss 2004; Cockburn and

others 1999) and results in substantial societal costs (Blaiss 2000). In addition, since the

nose is the gateway to the respiratory tract, rhinitis is associated with symptoms arising

from the eyes (Hom and Bielory 2013), sinuses (Slavin 1998), middle ear (Doyle 2002), the

nasopharynx and lower airways (Passalacqua and others 2004). Both AR and non-allergic

rhinitis (NAR) are risk factors for the development of asthma (Barry 2000).

Recent advances in rhinitis include evidence for local allergic rhinitis, the demonstration of

the greater effectiveness of combination therapy, the concept of SCUAD, severe chronic

upper airways disease, and of rhinitis control.

All patients presenting with nasal symptoms require appropriate treatment based on an

accurate diagnosis. These guidelines for the management of patients with rhinitis are

intended to facilitate this. Evidence for the recommendations was obtained by using

electronic literature searches using the primary keyword – rhinitis. Further searches were

carried out by combining this search term with allergy, conjunctivitis, non-allergic,

epidemiology, occupational, concordance, adherence, compliance, comorbidities,

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vasomotor, idiopathic, neurogenic, asthma, immunotherapy, anti-IgE, sublingual

immunotherapy (SLIT), corticosteroid, antihistamine, anti-leukotriene, ipratropium bromide,

decongestant, cromoglicate, carbon dioxide, pharmacotherapy, complementary medicine,

alternative medicine, homeopathy, hypnotherapy, acupuncture, acupressure, herbal

medicine, allergen avoidance, cat, house dust mite(HDM), control, quality of life, anti-IgE,

child, pregnancy, lactation, surgery, turbinectomy, aspirin, economics.

Each article was reviewed for suitability for inclusion in the guideline. The recommendations

were evidence graded, see appendix A (British Thoracic Society 2003; Shekelle and others

1999). During guideline development a web-based system was used to allow consultation

with all BSACI members. The draft guidelines were amended by the Standards of Care

Committee (SOCC) after careful consideration of all comments and suggestions. Where

evidence was lacking, a consensus was reached among the experts on the committee.

Conflicts of interest were recorded by the SOCC; none jeopardized unbiased guideline

development.

Executive summary and recommendation

Allergic rhinitis

Is common and affects over 20% of the UK population

Affects quality of life, school and work attendance, and performance

Is diagnosed by history and examination backed up by specific allergy tests

Is a risk factor for the development of asthma

Topical nasal corticosteroids are the treatment of choice for moderate to severe disease

(Grade of recommendation=A)

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Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more

effective than either alone and provides second line treatment for those rhinitis poorly

controlled on monotherapy (Grade B)

Treatment of rhinitis from retrospective studies is associated with benefits for asthma

(Grade of recommendation=A)

Immunotherapy is highly effective in selected cases (Grade of recommendation=A)

Non-allergic rhinitis

Is a risk factor for the development of asthma.

Has a variety of causes.

May be eosinophilic and steroid- responsive or neurogenic and non- inflammatory.

May be a presenting complaint for systemic disorders such as Wegener’s, Churg-Strauss and

sarcoidoisis.

Infective rhinitis

Can be caused by viruses, and less commonly by bacteria, fungi and protozoa.

Is often more severe in allergic patients especially if infection occurs at the time of allergen

exposure.

DEFINITIONS / CLASSIFICATION

Definitions

Rhinitis describes inflammation of the nasal mucosa but is clinically defined by symptoms of

nasal discharge, itching, sneezing and nasal blockage or congestion. When the conjunctivae

are also involved, the term rhinoconjunctivitis is more accurate. Involvement of the sinus

linings in more severe disease is known as rhinosinusitis.

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Rhinitis has multiple phenotypes, usually divided into allergic, non-allergic and infective.

Mixed forms exist. This document concerns itself predominantly with the evidence- rich

area of AR.

Classification of AR.

The WHO ARIA workshop ‘Allergic Rhinitis and its impact on Asthma’ (Bousquet and others

2001) classification of AR based on frequency and severity of symptoms (Fig. 1) has been

validated (Demoly and others 2003a). Additionally clinical classification into seasonal and

perennial rhinitis is useful in UK practice for diagnosis and allergen specific therapy. Triggers

for AR are shown in Table 1.

Infective rhinitis

Any cause of congestion of the nasal mucosa can lead to occlusion of the sinus ostia,

predisposing to rhinosinusitis, and/or eustachian tube dysfunction. The causes and disease

patterns of infective rhinitis are summarised in Table 2.

Non-allergic rhinitis

The numerous diagnoses in this category need to be borne in mind for patients with

negative skin prick tests (SPTs). Table 3 summarizes the causes and disease patterns of NAR.

EPIDEMIOLOGY

The prevalence of allergic rhinitis in the UK has been reported as 10.1% and 15.3% in 6-7

and 13-14 year olds, respectively (Asher and others 2006), and a study combining

questionnaire and clinical assessment, including analysis of allergen-sensitisation, estimated

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prevalence in UK adults at 26% (Bauchau and Durham 2004). Peak prevalence appears to

occur in the 3rd and 4th decades (Blomme and others 2013; Eriksson and others 2012), with

some evidence for remission in allergic sensitisation during adult life (Warm and others

2012).

The prevalence of allergic rhinitis in the UK and Western Europe has increased dramatically

over the past 4-5 decades (Braback and others 2004; Gupta and others 2007). Some studies

suggest a plateau may have been reached (Asher and others 2006; Bjorksten and others

2008; Braun-Fahrlander and others 2004; Gupta and others 2007), whilst others report

continued increases since the 1990s (Duggan and others 2012; Ghouri and others 2008;

McNeill and others 2009). There is a male preponderance before adolescence (Alm and

others 2011; Alm and others 1999; de Bot and others 2009; Duggan and others 2012),

reversing post-adolescence (Eriksson and others 2012; Kellberger and others 2012; Mai and

others 2014). Worldwide, there appears to be a correlation between economic and

industrial development and the prevalence of allergic rhinitis (Asher and others 2006;

Katelaris and others 2012); post-communist Eastern Europe has seen accelerating

occurrence (von Mutius E. and others 1998). Local allergic rhinitis, confirmable only by nasal

provocation, has been found to have a prevalence of over 25% in some centres (Rondon and

others 2012).

Rhinitis is strongly associated with asthma: 74-81% of asthmatics report symptoms of

rhinitis (Leynaert and others 2004); rhinitis, both allergic and non-allergic, is a strong risk

factor for new-onset asthma (Guerra and others 2002; Shaaban and others 2008). Most

epidemiological studies report on allergic rhinitis, fewer have investigated non-allergic

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rhinitis. A prevalence ratio of allergic to non-allergic rhinitis of 3:1 has been suggested

(Settipane 2009).

AETIOLOGY

An overview of aetiological factors and associations of rhinitis is given in table 4. Genetic

predisposition is probably the most important factor in its development, but identification

of specific susceptibility genes has proved difficult. The development of large scale, genome

wide association studies (GWAS) has allowed identification of several candidate loci and

genes for asthma and atopic dermatitis (Moffatt and others 2010; Moffatt and others 2007;

Paternoster and others 2012; Portelli and others 2014). To date, only one such GWAS has

been carried out for AR (Ramasamy and others 2011). Of note, classical genetic change (i.e.

change in DNA nucleotide sequence) is unable to account for the rapid increase in

prevalence of AR seen in recent years, suggesting environmental factors (and possible gene-

environment interactions) are important. Epidemiological evidence suggests various factors

are involved: smaller family size, urban environments, and reduced exposure to infectious

disease are some of the best supported candidates, and appear to have particular effect

during early life (Matricardi and others 2002; Riedler and others 2001; Strachan 1989a;

Strachan 1989b). Epigenetic modifications, such as DNA methylation, may be involved in the

mechanism of gene-environment interactions in allergic diseases (Kabesch 2014).

PATHOPHYSIOLOGY

The basic mechanisms of allergic rhinitis are illustrated in Figure 2. Sensitised patients with

allergic rhinitis have IgE antibodies for specific allergen(s) bound to receptors on the surface

of mast cells. On re-exposure to the specific allergen(s), cross-linking of adjacent IgE

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molecules occurs, and mast cell degranulation results. Pre-formed mediators such as

histamine stimulate sensory nerve endings within seconds, causing itch and sneezing, and

promote dilatation of local vasculature and glandular secretion, causing obstruction and

rhinorrhoea, respectively. Newly-synthesised mediators, including leukotrienes, as wells as

chemokines and cytokines contribute to a delayed eosinophil and Th2 T-cell predominant

inflammation, the late phase response, characterised by nasal obstruction and hyper-

reactivity (Hansen and others 2004).

Additional mechanisms are likely to be relevant. These include neuro-immune interactions,

such as release of neuropeptides (substance P, calcitonin gene-related peptide) and

neurokinins from sensory nerve endings in response to inflammatory mediators (Van

Gerven L. and others 2012). The role of the epithelium, particularly its interaction with

newly-defined type 2 innate lymphoid cells (ILC2), has been scrutinised in murine asthma

and allergy models (Licona-Limon and others 2013; Lloyd 2010) as well as in human asthma

(Saglani and others 2013; Ying and others 2008). Further research is needed to confirm the

relevance epithelial-derived cytokines such as TSLP, IL-33 and IL-25 as well as ILC2 cells in

allergic rhinitis (Scadding 2014).

Non- allergic rhinitis, NAR ( also called non-allergic, non- infectious rhinitis NINAR , or

idiopathic rhinitis)

This is a diagnosis of exclusion in patients negative for systemic IgE, when the many other

causes of rhinitis, have been ruled out (Table 3). The terminology of vasomotor rhinitis,

which is inaccurate, has been dropped in the UK. There remain many questions about the

nature of NAR (Bousquet and others 2008).

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Pathophysiology.

Unfortunately much of the evidence around NAR is of poor quality because of inadequate

patient selection. However reliable data suggests at least two subgroups: one with nasal

inflammation on histology (Powe and others 2001), the other without inflammation or local

IgE production (Kleinjan and others 2000). The former includes local allergic rhinitis and

non- allergic rhinitis with eosinophilia( NARES ); some of this group are aspirin / NSAID

sensitive (Szczeklik and others 2000).

The non-inflammatory rhinitis subjects are thought to suffer from a dysfunction of the

autonomic nerve supply to the nasal mucosa (an imbalance in favour of the

parasympathetic system, resulting in gland hypersecretion and loss of the normal

sympathetic vasomotor tone) and/or a dysfunction of non-adrenergic, non-cholinergic

unmyelinated sensory C-fibres, with an excess of neuropeptide-mediated responses

(Settipane and Kaliner 2013; Van Gerven L. and others 2012).

Triggers are non-allergic (Table 3) and symptoms continue despite a change of location.

Mixed forms of rhinitis, with inflammatory and neuronal elements are thought to occur in a

high proportion of sufferers (Bernstein 2010), with mediators such as histamine and

substance P irritating nerve endings in the mucosa. This combined with antidromic reflexes

may be the basis of rhinitis – induced conjunctival symptoms and bronchial hyper-

reactivity.

Co-morbid associations of rhinitis

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AR coexists with other organ-specific allergic disorders,such as asthma and atopic

dermatitis, especially in children. It also has other associated comorbid disorders which can

be subdivided into

a)other allergic diseases,e.g. asthma, atopic dermatitis ,food allergy,oral allergy syndrome,

anaphylaxis, eosinophilic oesophagitis;

b) problems related anatomically to the nose: conjunctivitis, rhinosinusitis, hyposmia,

middle ear problems, throat and laryngeal effects;

c) Sleep problems and secondary effects of symptoms on concentration, mood and

behaviour, such as depression, anxiety, sexual dysfunction, attention deficit hyperactivity

disorder, reduced driving ability.

d) Others- where cause and effect is uncertain: migraine, high arched palate, or where the

co- morbidity may cause rhinitis symptoms: e.g. gastro- oesophageal reflux, hypothyroidism.

Table 5 shows evidence for the major co-morbidities.

The most important co-morbidity is asthma: not only is rhinitis a risk factor for subsequent

asthma, but the majority of asthma sufferers have concomitant rhinitis, poor control of

which is a risk factor for asthma exacerbations (Clatworthy and others 2009; de Groot and

others 2012; Lasmar and others 2006; Price and others 2005; Thomas and others 2005).

Occupational rhinitis

Occupational rhinitis, which can be allergic or non-allergic, describes abnormalities of the

nasal mucosa mediated by airborne substances in the work environment. It is distinct from

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work-exacerbated rhinitis which refers to individuals with pre-existing rhinitis who

experience an exacerbation of symptoms due to workplace exposures.

There are over 300 agents that can give rise to occupational rhinitis and these are the same

as those that induce occupational asthma. These agents are classified as either high

molecular weight (HMW) (>5kDA) or low molecular weight (LMW) agents (<5kDA)(Table 6)

(Bernstein and others 2006). HMW agents are protein allergens derived from plants or

animals e.g. flour, latex, laboratory animals and elicit specific IgE (Raulf and others 2014).

Evidence of sensitisation to HMW agents will usually be seen on skin testing or serum

specific IgE. LMW agents can either cause mucosal inflammation either via airway immune

sensitisation, e.g. di-isocyanates and glutaraldehyde or via irritant exposures e.g. chlorine

and ammonia. An asymptomatic latency period of exposure lasting weeks to years often

precedes symptoms of occupational rhinitis to LMW agents (Hox and others 2014).

Occupational rhinitis is three times more frequent than occupational asthma but the two

conditions frequently occur together (Karjalainen and others 2003; Siracusa and others

2000). Occupational rhinitis generally precedes, and may be a risk factor for, occupational

asthma. The risk of occupational asthma is highest in the year after the development of

occupational rhinitis (Cortona and others 2001; Karjalainen and others 2003). (level of

evidence 2-). The early identification of a causative occupational agent and the avoidance of

exposure are important measures for the management of occupational rhinitis and

prevention of progression to occupational asthma (Colloff and others 1992; Filon and

Radman 2006; Kronqvist and others 1999; O'Meara and others 2005). (level of evidence = 2+

+; grade of recommendation=B)

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Diagnosis is based on a detailed history, symptomatic diary cards, improvement of nasal

symptoms during weekends and holidays, skin prick testing and measurement of specific IgE

when appropriate. Where available the gold-standard for diagnosis remains nasal

provocation testing.

Latex is a cause of both occupational rhinitis and asthma. Prevention of latex allergy by

removing powdered gloves or substituting non-latex ones is essential. All healthcare

environments should have a latex policy (Filon and Radman 2006; Hemery and others 2004).

(Level of evidence=2+ and 4; Grade of recommendation=D, C for adults and children with

perennial rhinitis or adults and children with latex allergy.)

DIAGNOSIS OF RHINITIS

History

A detailed history focusing on the severity of individual symptoms of rhinitis is required for

accurate diagnosis. The patient is asked to list their main symptoms in order of priority and

this usually produces a short list of differential diagnoses. Longstanding symptoms can also

result in systemic manifestations affecting quality of life such as difficulty sleeping, fatigue,

and impaired concentration leading to reduced productivity.

Symptoms

Nasal Symptoms

Sneezing, itchy nose, itchy palate

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Itching indicates a likely diagnosis of allergic rhinitis and asking whether the symptoms are

intermittent or persistent may provide a clue to the allergic cause. However, this is not a

substitute for specific allergen testing.

Seasonal at the same time each year? – pollens or mould spores

At home?- pets or house dust mite

At work? - occupational allergens

On holiday? – remission suggests an environmental or allergic cause

Rhinorrhoea

Rhinorrhoea is either anterior or leads to a post nasal drip:

Clear - infection unlikely

Unilateral - is uncommon and cerebrospinal fluid (CSF) leak should be excluded

(Marshall and others 2001)

Coloured

o yellow - allergy or infection

o green - usually infection

o blood tinged

unilateral – tumour, foreign body, nose picking or misapplication of nasal spray

bilateral – misapplication of nasal spray, granulomatous disorder, bleeding

diathesis, infection, nose picking.

Nasal obstruction

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Obstruction may be partial or complete with the severity often correlating with systemic

manifestations such as interrupted sleep.

Bilateral –most likely rhinitis or nasal polyps but maybe septal (sigmoid) deviation

Unilateral – usually septal deviation but also consider foreign body, antrochoanal polyp

and tumours

Alternating – generalised rhinitis exposing the nasal cycle (Flanagan and Eccles 1997)

Nasal crusting

Severe nasal crusting especially high inside the nose is an unusual symptom and requires

further investigation. Consider:

chronic rhinosinusitis (Jennings and others 1998)

nose picking

Wegener’s granulomatosis, sarcoidosis

other vasculitides

ozaena (wasting away of the bony ridges and mucous membranes inside the nose)

non-invasive ventilation

rarely, topical steroids may cause crusting

Cocaine abuse

Eye symptoms

Eye symptoms associated with allergic rhinitis and particularly with seasonal rhinitis include

intense itching, redness and swelling of the white of the eye (i.e. hyperaemia and oedema of

the conjunctival surfaces), and watering, which may momentarily blur the vision. Lid

swelling and (in severe cases) periorbital oedema are enhanced by eye rubbing.

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Lower respiratory tract symptoms

Cough, wheeze, shortness of breath- can occur with rhinitis alone since bronchial hyper-

reactivity can be induced by upper airway inflammation (Laitinen 1974; Laitinen and

Kokkola 1974; Townley and others 1965).

Disorders of the upper and lower respiratory tract often coexist:

Most asthmatics have rhinitis – see section on rhinitis and asthma

In asthma with aspirin sensitivity – 36-96% have upper airway disease, usually nasal

polyps with rhinosinusitis, a few have rhinitis (Settipane and Chafee 1977).

Other Symptoms

Other symptoms such as snoring, sleep problems, repeated sniffing or a nasal intonation of

the voice can be caused or exacerbated by nasal obstruction and rhinorrhoea from any

cause. In some patients with seasonal allergic rhinitis, oral allergy syndrome is triggered by

ingestion of cross-reacting antigens in some fruits, vegetables and nuts (Ortolani and others

1988).

Family history

A diagnosis of allergic rhinitis is more likely when rhinitis is seasonal, in the presence of

asthma or a family history of atopy (VAN ARSDEL PP and MOTULSKY 1959).

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Social history

In order to assess possible allergen and irritant exposure a full history of housing conditions,

presence of pets or other contact with animals, occupation or schooling and, in young

children, feeding details should be obtained.

Drugs

A number of drugs can cause or aggravate rhinitis symptoms and therefore a drug history

should include details of the use of alpha- and beta-blockers and other anti-hypertensives,

aspirin and other non-steroidal anti-inflammatory drugs, oral contraceptives as well as

topical sympathomimetics (see table 3). It is also important to enquire about the efficacy of

previous treatments for rhinitis and details of how they were used and for how long.

Occupation

When symptoms occur at work and improve when away from work or on holiday an

occupational irritant or allergen triggering rhinitis should be suspected.

Examination

Visual assessment

Allergic salute and/or horizontal nasal crease across dorsum of nose supports a diagnosis

of allergic rhinitis

Chronic mouth breathing

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An assessment of nasal airflow – (e.g. metal spatula misting in young children)

Depressed nasal bridge – post surgery, Wegener’s granulomatosis or cocaine misuse

Widened bridge; polyps (see also BSACI guideline on rhinosinusitis and nasal polyposis;

(Scadding and others 2008))

Purple nasal tip due to sarcoidosis

Anterior rhinoscopy

Hypertrophic, pale and boggy inferior or middle turbinates suggest inflammation, but

nasal appearance may be normal

Presence or absence of clear, coloured or purulent secretions

Presence or absence of nasal polyps, but it may not be possible to see small ones or if

they are confined to the sinuses. Larger polyps can be seen in the nasal vestibule

sometimes extending as low as the nares and can be distinguished from the inferior

turbinate by their lack of sensitivity, yellow/ grey colour and the ability to get between

them and the side wall of the nose.

Yellow sub-mucosal nodules with a cobblestone appearance suggest sarcoidosis (Fergie

and others 1999).

Crusting and granulations raise the possibility of vasculitis.

Septal perforation may occur after septal surgery or due to chronic vasoconstriction

(cocaine, alpha agonists), Wegener’s granulomatosis, nose picking and rarely due to

steroid nasal sprays.

INVESTIGATIONS

Objective measures of nasal airway

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Objective measurements of the nasal airway are not made in routine clinical practice but

can be useful when allergen or aspirin challenges are undertaken and may be helpful when

septal surgery or turbinate reduction are being contemplated.

Peak nasal inspiratory flow

Measurement of peak nasal inspiratory flow (PNIF) provides a simple and inexpensive

method for determining nasal airway patency using a nasal inspiratory flow meter. The

results are reproducible and correlate with rhinoscopic evidence of rhinitis but not with

symptom scores (Starling-Schwanz and others 2005). The technique is most useful for

comparing changes in airway patency within the same subject, although some normative

data is now available (Ottaviano and others 2006).

Acoustic Rhinometry

Acoustic rhinometry can be used to measure changes in mucosal congestion using reflected

sound. The technique is based on the physical principle that sound in the nasal cavity is

reflected by changes in acoustic impedance caused by changes in cavity dimensions. The

change in acoustic impedance between the incident wave and reflected sound waves is

proportional to the cross-sectional area. The method requires standardization and

considerable experience to interpret and obtain reproducible results. Guidelines for its use

are published (Hilberg and Pedersen 2000).

Rhinomanometry

Rhinomanometry allows an estimation of nasal resistance from pressure-flow relationships

and is difficult to perform reproducibly but still regarded by some as the most accurate

measure of nasal airway patency. With anterior rhinomanometry, the pressure sensor is

placed at the tip of each nostril and resistance measured in each nostril separately. With

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posterior rhinomanometry the pressure sensor is placed in the back of the nasal cavity and

total nasal airway resistance is determined. The technique requires expensive equipment

and considerable experience in interpretation (Clement 1984).

Nasal endoscopy

Used in specialist centres, this is more specific than rhinoscopy and alters the diagnosis in up

to a fifth of patients with nasal disease (Hughes and Jones 1998).

Allergen specific IgE can be detected with skin prick tests (SPTs) or by serum immunoassay.

Skin prick tests

Skin prick tests (SPT) should be carried out routinely in all cases in order to determine if the

rhinitis is allergic or non-allergic. Injectable adrenaline should be available, but is unlikely to

be needed.

Must be interpreted in the light of the clinical history. At least 15% of people with a

positive skin prick test do not develop symptoms on exposure to the relevant allergen

(Droste and others 1996).

Have a high negative predictive value.

Suppressed by antihistamines, tricyclic antidepressants and topical but not oral steroids

(Taborda-Barata and others 1996).

Are inadvisable outside specialist allergy clinics if the patient has a history of

anaphylaxis.

Serum total and specific IgE

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Serum specific IgE may be requested when skin tests are not possible or when the SPT

together with the clinical history give equivocal results.

Total IgE alone can be misleading but may aid interpretation of specific IgE.

Allergen specific IgE correlates with the results of skin prick tests and nasal challenges

although there are exceptions.

Currently available SPTs and immunoassays show similar sensitivity for house dust mite

(HDM), but SPTs are more sensitive to other inhalant allergens such as cat epithelium,

mould and grass pollen (Gleeson and others 1996).

Routine laboratory investigations

Other investigations to help with the initial management of patients with rhinitis are guided

by the findings from the history, examination and results of skin prick tests. Examples of

routine laboratory investigations include:

Full blood count (FBC) and differential white cell count

C-reactive protein (CRP)

Nasal smear/brushing for eosinophils

Microbiological examination of sputum and sinus swabs

Nasal secretions-CSF asialotransferrin for CSF rhinorrhoea

Urine toxicology when cocaine abuse is suspected

Olfactory tests

The University of Pennsylvania Smell Identification Test (UPSIT) is well validated, can identify

malingerers (Doty and others 1984) and is accepted for legal cases.

Cytology

The techniques for obtaining cells for cytology in secretions, lavage, scraping, cotton

pledgelets or brushings has not been standardised, nor have the criteria for evaluating cell

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counts (Romero and Scadding 1992). Nevertheless the presence of eosinophils implies

inflammation and may be helpful in predicting response to corticosteroids.

Exhaled nitric oxide (eNO)

Exhaled nitric oxide (FeNO = fractional exhaled nitric oxide) measurement can be useful

clinically in the diagnosis and monitoring of asthma. Normal levels are less than 20ppb, but

become elevated in eosinophilic lower respiratory tract inflammation (Prieto and others

1994).

Radiology

Radiology is not routinely recommended for rhinitis patients.

Nasal challenge

Is not routinely available outside specialist centres.

There is no standardised methodology.

Asthmatic reactions can occur.

May be useful to confirm aspirin sensitivity.

May be useful in patients with an unclear history and negative or equivocal tests for

allergen specific IgE or when the trigger is not IgE-mediated.

Has a role in occupational allergic rhinitis, where there is discrepancy between history

and when there are potentially important occupational implications.

Can be used to assess nasal hyper- reactivity to histamine or metacholine in a research

setting.

Tests for asthma

Measurements of lung function should be considered in all patients with persistent rhinitis

e.g. (peak expiratory flow rate (PEFR) or spirometry as detailed in the British Thoracic

Society guidelines on the management of asthma (British Thoracic Society 2003).

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ENT referral

Patients with unilateral symptoms, heavily blood stained discharge, pain, or orbital cellulitis

need ENT referral, urgently for orbital swelling, redness and pain. Those with structural

abnormalities, such as septal deviation, which render nasal therapy difficult, should also be

seen by a surgeon.

TREATMENT (see figure 3)

Allergen avoidance

Allergen avoidance clearly works in rhinitis - in the case of seasonal allergic rhino-

conjunctivitis patients are symptom-free outside the pollen season. For patients with

allergic rhinitis/ rhinoconjunctivitis who are sensitised to house dust mite, the situation is

complicated by the difficulties of reducing exposure to mites, and evidence from

randomised studies is summarised in Table 7. For occupational allergic rhinitis, complete

avoidance of exposure to the causal agent is recommended (Raulf and others 2014)).

Irritants such as smoke, traffic pollution, etc. can worsen rhinitis symptoms and should be

avoided, where possible.

House dust mite.

After pollen, HDM is the most common sensitisation found in patients with

rhinoconjunctivitis in the UK and sensitisation to mites is associated with perennial

symptoms. Many methods have been developed which aim to reduce exposure to mite

allergens in the home; those that have been tested in randomised trials of rhinitis include air

filtration (such as HEPA filters), chemicals to kill mites (acaricides) and barriers to keep mites

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and allergen from reaching patients (such as mattress encasings) (Recer 2004; Terreehorst

and others 2003). A summary allergen avoidance measures with grades of evidence is

presented in Table 7 Acardust studies to be added to this table; studies published by 2009

were included in the updated Cochrane systematic review (Geller-Bernstein and others

1995; Nurmatov and others 2012).

Pollen avoidance in seasonal allergic rhinitis.

Nasal filters have been shown to reduce symptoms of AR and allergic conjunctivitis

significantly during the ragweed and grass pollen seasons (O'Meara and others 2005). A

number of other measures are often recommended to patients with pollen allergy to

minimize symptoms but these are based on expert consensus rather than clinical trial data

(Table 7). Haymax™ balm decreases levels of allergen entering the nose by a third; it is not

known whether other substances such as petroleum jelly have the same effect (Kennedy

and others 2012). In a DBRPC study the application of a cellulose powder (Nasaleze™)

resulted in significant reductions in severity scores for sneezing, runny nose, stuffy nose and

symptoms from eyes and lower airways and no clinically significant adverse effects were

reported (Aberg and others 2014). Ozturk and colleagues found in a randomised controlled

study that patients wearing sunglasses had significantly decreased ocular symptoms and

antihistamine use (Ozturk and others 2013).

Pet allergens

For patients with allergic rhino-conjunctivitis who are sensitized to and symptomatic on

contact with pets such as cats, dogs and horses, avoidance of the animal is clearly beneficial

and should be advised. For those who wish to keep pets to which they are sensitized, there

23


is limited information from randomized studies on which to base recommendations

(summarized in Table 7). Bjornsdottir (Bjornsdottir and others 2003) found in a randomised

controlled study that reducing cat allergen in the environment of cat allergic patients over

an 8 months period was leading to significant improvement in nasal inspiratory flow rate

and symptoms. However, trials of brief cat removal are ineffective (Colloff and others 1992).

A number of measures to minimize cat allergen levels at home are recommended (Table 7).

Laminar airflow used nocturnally improved quality of life, airway inflammation and systemic

allergy to Fel d1, the major cat allergen, in a double blind study in children with persistent

atopic asthma (Boyle and others 2012). Recently it has been shown to reduce allergen

exposure (Gore and others 2015).

Saline irrigation

Hypertonic saline irrigation has been shown to be effective in children for the short term

treatment of hay fever (Chen and others 2014; Marchisio and others 2012), and isotonic

saline is well tolerated in children as young as 2 years (Jeffe and others 2012). In a review in

2013 (Dunn and others 2013) the high volume, low pressure device was claimed to be the

most effective though it warned against microbial contamination and reported 2 cases of

primary amoebic meningoencephalitis. However, a meta -analysis (Hermelingmeier and

others 2012) determined that despite heterogeneity of type, amount, frequency and

solution, isotonic saline irrigation had a positive effect on all investigated outcome

parameters (nasal symptom scores, medicine consumption, mucociliary clearance time and

quality of life) in both adults and children with allergic rhinitis, and it is well tolerated,

inexpensive, easy to use and there was no evidence of adverse effect to health with regular

use.

24


Pharmacotherapy

Allergen and irritant avoidance is difficult and many rhinitis sufferers continue to have

persistent symptoms, the nature of which should determine the selection of medication.

Available treatments and their effects upon individual symptoms are detailed in Table 8. All

have Grade A level of recommendation. Following exact diagnosis and classification

according to disease severity, therapy using a stepwise pharmacotherapeutic approach

should be undertaken. A combination of treatments is often needed for more severe

disease and it is here that the option of immunotherapy should also be considered (figure

3).

Antihistamines

Antihistamines are available as oral, intranasal and ocular preparations.

All demonstrate clinical efficacy. It is important to use a drug that is considered safe for the

current situation (i.e. such as pregnancy) with the least prominent adverse effect profile.

Oral antihistamines are classified into first and second generation groups (Table 9).

First generation anti-histamines are contraindicated due to sedation and cognitive

impairment which can worsen driving and examination results already impaired by rhinitis

(Walker and others 2007; Weiler and others 2000).

Second generation antihistamines are long acting, and more selective for peripheral over

central H1 receptors due to poor penetration of the blood-brain barrier. They are largely

non-sedating and have no clinically significant anti-cholinergic activity at therapeutic doses,

25


although there is variation in individual susceptibility to such effects (Shamsi and Hindmarch

2000)

Oral H1- antihistamines (Table 9)

Reduce mean daily rhinitis symptom scores (in absolute terms) by an estimated 7%

versus placebo (Wilson and others 2004a).

Act predominantly on neurally-mediated symptoms of itch, sneeze and rhinorrhoea.

Have modest effects on nasal congestion (Canonica and others 2007; Ciprandi and

others 2004; Ciprandi and others 2001; Hore and others 2005; Nayak and Schenkel

2001; Patou and others 2006; van Steekelenburg J. and others 2002).

Reduce histamine driven symptoms such as itch (Dhand and Aminoff 2014) at sites

other than just the nose such as conjunctiva, palate and skin (Nelson 2003; Portnoy

and Dinakar 2004; Schwarzer and others 2004).

Regular therapy is more effective than ‘as needed’ use in persistent rhinitis (Ciprandi

and others 1997a; Leurs and others 2002).

Can significantly improve quality of life (Bachert and others 2004; Pariente and

others 1997).

Acrivastine has the fastest onset of action, but needs to be used 8 hourly; fexofenadine is

the least sedating oral antihistamine with a wide therapeutic index.

Adverse Effects:

Second generation antihistamines

26


Terfenadine and astemizole were implicated in deaths from ventricular fibrillation via QT

interval prolongation. There are no significant effects on QT prolongation at therapeutic

doses for loratadine, desloratadine, cetirizine, levocetirizine, rupatadine or fexofenadine.

Ebastine and mizolastine are cautioned in those with cardiac risk factors (Davila and others

2006).

Interaction with other medications is rare other than for mizolastine with certain anti-

arrhythmics, antibiotics and beta-blockers leading to an increased risk of arrhythmia.

Rupatadine should not be co-prescribed with known CYP3A4 inhibitors (Picado 2006).

Place in therapy

• First line therapy for mild to moderate intermittent and mild persistent rhinitis

• Addition to intranasal steroids for moderate/severe persistent rhinitis uncontrolled

on topical intranasal corticosteroids alone, particularly when excess neurogenic symptoms

are present (Juniper and others 1989; Ratner and others 1998; Simpson 1994).

Topical H1- antihistamines

Nasal

Azelastine nasal spray is the only available intranasal antihistamine in the UK.

Superior to oral antihistamines in attenuating rhinitis symptoms (Lee and Pickard 2007),

and in decreasing nasal obstruction (Horak 2008; Lieberman and others 2005).

Do not improve symptoms due to histamine at other sites, such as skin.

Rapid onset of action (15 minutes), faster than oral antihistamines (Horak and others

2006) Thus the drug can be used on demand as rescue therapy for symptom

breakthrough. Continuous treatment is however more clinically effective than on-

demand use (Ciprandi and others 1997b).

27


Can be effective in patients who have previously failed oral anti-histamines (LaForce and

others 2004). Treatment with both an intranasal and oral antihistamine confers no

additional advantage in alleviating nasal symptoms (LaForce and others 2004).

Less effective than an intranasal steroid in relieving the symptoms of allergic rhinitis

(Yanez and Rodrigo 2002).

Adverse Events

Local tissue irritation

Taste disturbance with azelastine (dysguesia)

Place in therapy

First line therapy for mild to moderate intermittent and mild persistent rhinitis.

When oral antihistamines are ineffective and before intranasal steroid use in less severe

disease.

Addition to intranasal steroids for moderate/severe persistent rhinitis uncontrolled on

topical intranasal corticosteroids alone.

Corticosteroid therapy

Intranasal corticosteroids (INS)

Topical corticosteroids are the mainstay of anti-inflammatory and immunoregulatory intervention in

allergic rhinitis. All current preparations are clinically efficacious. Other factors which need

consideration are systemic drug bioavailability, overall safety and cost (Bielory and Bielory 2014).

Ease of device use and sensory attributes of the formulation may improve compliance.

INS reduce all symptoms of rhinitis by about 17% greater than placebo, with a variable effect on

associated allergic conjunctivitis (Hong and others 2011; Keith and Scadding 2009).

28


Meta-analysis shows that INS are superior to both oral antihistamines or leukotriene receptor

antagonist alone on all aspects of allergic rhinitis (Weiner and others 1998; Wilson and others

2004a) (Grade Ia).

INS reduce nasal congestion (Weiner and others 1998)

Onset of action is 6-8 hours after the first dose, clinical improvement may not be apparent for a few

days and maximal effect may not be apparent until after two weeks (Weiner and others 1998).

Starting treatment two weeks prior to a known allergen season improves efficacy (Graft and others

1996).

Similar clinical efficacy for all INS, but bioavailability varies considerably (see Figure 4).

Systemic absorption negligible with mometasone furoate, fluticasone furoate and

fluticasone propionate, modest for the remainder, and high for betamethasone and

dexamethasone – these should be used short term only (Derendorf and Meltzer 2008;

Homer and Gazis 1999)

Long term growth studies in children using fluticasone propionate, mometasone furoate and

have reassuring safety data, unlike beclomethasone (Sastre and Mosges 2012; Skoner and

others 2000)

Concomitant treatment with CYP3A inhibitors such as itraconazole or ritonivir may increase

systemic bioavailability of intranasal corticosteroids. (Johnson and others 2006; Skov and

others 2002).

Adverse events

Local nasal irritation, sore throat and epistaxis affect around 10% of users.

Benzalkonium chloride is used as a preservative in several topical corticosteroids, and may

irritate the nose, but does not adversely affect mucociliary clearance (McMahon and others

1997). In patients with nasal irritation symptoms such as burning for example, a trial with a

benzalkonium free preparation, e.g. Rhinocort, Flixonase nasules is suggested.

29


Reduction of local adverse effects such as nasal crusting, bleeding and pain can probably be

achieved by correct use of the intranasal device, see figure 4a; (Grade of

recommendation=D).

Nasal drops are useful for severe obstruction and should be used in the ‘head upside down’

position in order to reach the ostiomeatal complex (OMC), see figure 4b.

Hypothalamic-pituitary axis suppression may occur when multiple sites are treated with

topical corticosteroids in the same person (e.g. skin, nose and chest) (Allen 2000).

Raised intra-ocular pressure has been described with INS (Bui and others 2005) and patients

with a history of glaucoma should be monitored closely (in collaboration with an

ophthalmologist or optometrist).

Place in Therapy

First line therapy for moderate to severe persistent symptoms (Bousquet and others 2001).

First line of therapy if presenting with severe nasal obstruction (Weiner and others 1998),

possibly combined with a short term nasal decongestant. In severe nasal obstruction steroid

drops or oral steroids should be used initially.

Addition to topical antihistamines in uncontrolled rhinitis- see below.

Combination Therapy

INS and oral preparations

INS demonstrate similar or greater efficacy to an oral antihistamine plus a leukotriene receptor

antagonist (Pullerits and others 2002a; Wilson and others 2001b). INS combined with an oral

antihistamine and leukotriene receptor antagonist together does not confer better clinical outcomes

compared to an INS alone in SAR (Di Lorenzo G. and others 2004).

INS and topical H1-antihistamine combination

30


Currently available as a combination spray containing azelastine and fluticasone propionate (FP),

Dymista leads to greater symptom improvement than using either agent alone in SAR (Carr and

others 2012a) (Grade A ). All symptoms of allergic rhinitis were significantly improved with onset of

action by 30 minutes (Meltzer and others 2012).

The combination approach leads to clinical improvement of symptoms days earlier than seen with

azelastine or FP monotherapy (Carr and others 2012a). Ocular symptoms of allergy were better

treated with the azelastine-fluticasone propionate combination spray rather than fluticasone

propionate or azelastine alone (Meltzer and others 2012). Efficacy over FP is demonstrated in

perennial allergic rhinitis (Price and others 2013).

Place in therapy

Combination of topical AH with INS should be used in patients when symptoms remain uncontrolled

on AH or INS monotherapy or on a combination of oral AH plus INS.

Systemic glucocorticoids

There are no trials of oral steroid use and efficacy in AR, though there is grade A evidence in chronic

rhinosinusitis with nasal polyposis where inflammation is more severe. Use is rarely indicated in the

management of allergic rhinitis except for:

Severe nasal obstruction

Short term rescue medication for uncontrolled severe symptoms when first presenting or to obtain

control during severe exacerbation despite compliance on conventional pharmacotherapy. It is

important to ensure intranasal steroid therapy is co-administered alongside oral steroids with or

without a short term decongestant spray to allow intranasal drug penetration (see below). There is

no definite consensus on the dose and duration of systemic steroid therapy. A suggested regime for

adults is 0.5mg per kg for 5-10 days. Oral preparations of steroids as a short course are

31


recommended over depot injectable preparations. Frequent oral steroid rescue should prompt

immunotherapy as a treatment option

Injectable corticosteroids

Injected preparations are not recommended

Compared to other available treatments the risk-benefit profile for intramuscular

corticosteroids is poor (Aasbjerg and others 2013; Nasser and Ewan 2001).

Decongestants

Decrease nasal congestion via vasoconstriction.

A paradoxical increase in nasal congestion secondary to rebound vasodilatation (rhinitis

medicamentosa) can occur (Scadding 1995a). The risk of this is patient -dependent with some

individuals vulnerable after 3 days of use so short term use is advised (Morris and others 1997; Yoo

and others 1997).

Intranasal decongestants

Topical formulations allow relief of nasal congestion within minutes, faster and with greater impact

than intranasal steroids (Barnes and others 2005; Baroody and others 2011a). A decongestant spray

may allow delivery of intranasal drugs beyond the inferior turbinates. For example oxymetazoline

and fluticasone furoate when used together further improved nasal congestion more than either

alone (Baroody and others 2011b).

INS plus decongestant combination

There is no licensed preparation in the UK at present.

32


Adverse events

Only short term use (generally less than 10 days) is recommended as risk of developing rebound

treatment resistant nasal congestion termed rhinitis medicamentosa increases with duration

(Scadding 1995b)

Intranasal decongestants are less likely to lead to rhinitis medicamentosa when used with minimal

frequency and alongside an intranasal steroid (Baroody and others 2011b).

Nasal irritation

May increase rhinorrhoea

Place in Therapy

Eustachian tube dysfunction when flying (evidence level D)

Children with acute otitis media to relieve middle ear pain /pressure (Evidence level D)

During or after URTI to reduce nasal/sinus congestion (Evidence level D)

To increase nasal patency before douching or intranasal administration of nasal steroids (ask HK)

Oral decongestants (pseudoephedrine)

Weakly effective in reducing nasal obstruction (Malm 1994).

Do not cause rebound effect on withdrawal but are less effective than topical preparations for nasal

obstruction (Naclerio 1998).

Effect lasts 30min - 6hrs or longer with slow-release preparations.

Adverse events

Hypertension

Interact with antidepressants

Insomnia

33


Agitation

Tachycardia

Place in Therapy

Not recommended.

Anti-leukotrienes

Anti-leukotrienes are of two kinds i) receptor antagonists (LTRAs, e.g. montelukast

and zafirlukast) (Scadding and Scadding 2010) and ii) synthesis inhibitors, e.g.

zileuton (unavailable in the UK).

There is a spectrum of individual responsiveness to LTRAs which is currently not

predictable (Fowler and others 2002; Mastalerz and others 2002; Sampson and

others 2000).

Therapeutic profile similar to antihistamines, with efficacy comparable to loratadine

in seasonal allergic rhinitis (Philip and others 2002). However, the response is less

consistent than that observed with antihistamines. LTRAs reduce the mean daily

rhinitis symptom scores by 5% more than placebo (Wilson and others 2004b).

Anti-leukotrienes are less effective than topical nasal corticosteroids (Philip and

others 2002; Pullerits and others 1999; Ratner and others 2003; Wilson and others

2001a).

Anti-leukotriene plus antihistamine combinations do not improve efficacy to a

clinically relevant extent compared to either drug used alone (Meltzer and others

2000; Nayak and others 2002; Wilson and others 2002; Wilson and others 2001c).

Combination of antihistamine and anti-leukotriene is no more effective than topical

corticosteroid alone (Di Lorenzo G. and others 2004; Pullerits and others 2002b).

34


May have a place in asthma patients with seasonal allergic rhinitis (Philip and others

2004).

Adverse events

Usually well tolerated; occasional headache, gastrointestinal symptoms or rashes.

Possible causal link between LTRA use and Churg-Strauss syndrome (Hauser and

others 2008; Nathani and others 2008). The association may relate more to steroid

withdrawal rather than a direct effect of the drug, although further long term

evaluation is needed.

Long term use has been associated with depression ( needs ref)

Place in Therapy

Montelukast is licensed in the UK for those with seasonal allergic rhinitis who also

have concomitant asthma (UK license for age > 6 months; Zafirlukast UK license>12

years).

May be useful in patients with asthma and persistent rhinitis

Topical Anti-cholinergic: Ipratropium bromide

Decreases rhinorrhoea but has no effect on other nasal symptoms (Grossman and

others 1995a; Kaiser and others 1998; Meltzer and others 1992; Tan and Corren

1995).

Needs to be used 3 times daily.

35


Regular use may be effective, particularly as an ‘add on’ for allergic rhinitis when

watery rhinorrhoea persists despite topical steroids and antihistamines (Dockhorn

and others 1999; Grossman and others 1995b).

Adverse Events

Dry nose and epistaxis (Wood and others 1995)

Systemic anti-cholinergic effects are unusual (Bronsky and others 1995)

o Urinary retention (Pras and others 1991)

o Glaucoma (in relation to inhaled drug in asthma) (De Saint and others 2000;

Hall 1994)

Caution advised in the elderly

Place in therapy

Patients with rhinorrhoea despite compliance with an INS or INS plus antihistamine.

Chromones (Sodium cromoglicate (=cromolyn) and nedocromil sodium)

Sodium cromoglicate and nedocromil sodium inhibit the degranulation of sensitized mast

cells, inhibiting the release of inflammatory and allergic mediators (Ratner and others 2002).

Sodium cromoglicate is weakly effective in rhinitis with some effect on nasal obstruction

(James and others 2003; Meltzer 2002). The spray needs to be used several times (3-4x) per

day.

Side Effects

Generally very well tolerated (including in pregnancy)

Local irritation

36


Rarely transient bronchospasm

Occasional taste perversion

Headache

Place in therapy

Children and adults with mild symptoms only and sporadic problems in season or on

limited allergen exposure (Hadley 2003). Useful for young children (< 3 years

old),pregnant females and steroid phobics.

Cromoglicate and nedocromil eye drops are useful in conjunctivitis as topical therapy

(James and others 2003; Owen and others 2004).

Ocular therapy

As with rhinitis, allergen avoidance is difficult to achieve: sunglasses reduce eye

symptoms (Ozturk and others 2013), but since some occur secondary to nasal

inflammation complete protection is impossible . The ocular manifestations of

seasonal rhinoconjunctivitis can often be suppressed by oral antihistamines, usually

H1 receptor antagonists, and by intra-nasal agents, including corticosteroids,

antihistamines and combination products. However they are often better treated

selectively using topical therapy in eye drop form. Mast cell stabilisers such as

sodium cromoglicate, nedocromil sodium and lodoxamide are generally effective and

safe (Owen and others 2004). Antihistamines such as azelastine, emedastine and

epinastine may be preferred by some patients (Glacy.J and others 2013). A drug with

both mast cell stabilising and antihistaminic properties, olopatadine, is often

effective and well tolerated, and has the advantage of twice daily application, which

particularly suits contact lens wearers. The place of topical NSAIDs such as diclofenac

sodium is more difficult to define. Some patients find that tear supplement drops

37


(‘artificial tears’) provide a good measure of symptomatic relief. Topical steroids are

effective in suppressing inflammation but can have potentially sight-threatening

adverse effects including ocular hypertension / glaucoma, cataract, and the

enhancement of infection. If indicated, e.g. for vernal conjunctivitis, use should be

supervised by an ophthalmologist. Immunotherapy, where indicated, is effective for

ocular symptoms.

Immunotherapy

Allergen immunotherapy involves the repeated administration of allergen extracts in order

to improve symptoms, reduce medication requirements and improve quality of life of

allergy sufferers (Bousquet and others 1998; Canonica and others 2014; Passalacqua and

Durham 2007). It is indicated in patients with IgE-mediated allergic rhinoconjunctivitis in

whom allergen avoidance is not possible or undesirable and who fail to respond adequately

to anti-allergic drugs and/or develop unacceptable side effects on treatment (Walker and

others 2011).

Subcutaneous injection immunotherapy (SCIT) has been shown to be effective for both

seasonal rhinitis due to pollens (Cochrane meta-analysis (Calderon and others 2007)

evidence level 1++) and in patients with perennial allergy and sensitivity to house dust mite

((Eifan and others 2013), evidence level 1+). There are few randomised controlled trials of

immunotherapy for cat allergy ((Alvarez-Cuesta and others 1994; Varney and others 1997),

level 1+). SCIT requires weekly updosing regimens followed by 4-6 weekly maintenance

injections for 3-5 yr. In view of the risk of systemic allergic side effects that include

occasional anaphylaxis, SCIT should only be given in specialist clinics by trained personnel

38


and with immediate access to adrenaline and resuscitative measures (Alvarez-Cuesta and

others 2006).

Sublingual Immunotherapy

Sublingual immunotherapy (SLIT) has emerged as an effective and safe alternative to the

injection route in adults and children for the treatment of seasonal allergic rhinitis

with/without seasonal asthma (Canonica and others 2014). Cochrane meta-analysis

(Radulovic and others 2010) and several recent large randomised controlled trials in Europe

and in USA of sublingual tablet formulations have confirmed efficacy in patients with grass

pollen allergy (Bufe and others 2009; Cox and others 2012; Dahl and others 2008; Didier and

others 2007; Halken and others 2010; Maloney and others 2014) and in patients with

ragweed hay fever ((Creticos and others 2014; Creticos and others 2013), evidence level 1+

+). In contrast, the evidence for efficacy of SLIT in house dust mite-induced rhinitis,

particularly in children, is far less convincing, although several trials are in progress.

Sublingual immunotherapy is well-tolerated, with side effects largely confined to local

itching and swelling in the mouth such that after supervision of the first dose by the

prescribing physician with a one hour period of observation, SLIT may be self-administered

daily at home. There have been rare isolated case reports of systemic reactions after

sublingual immunotherapy (Makatsori and Calderon 2014) but these should be considered

in the light of an excellent safety record in many large controlled trials and extensive post-

registration experience with SLIT preparations. The subcutaneous and sublingual routes are

compared in general terms in table 10.

Long term benefits

In contrast to anti-allergic drugs, immunotherapy is the only treatment that has potential to

offer disease modification with longterm remission for several years after its

39


discontinuation. This has been demonstrated for subcutaneous immunotherapy (Durham

and others 1999) and recently confirmed for SLIT for seasonal grass allergy (Didier and

others 2013; Durham and others 2012). One randomised controlled trial of subcutaneous

immunotherapy in children with seasonal rhinitis showed a 2-3 fold reduction in progression

to physician-diagnosed asthma, an effect that persisted for 10 years (Jacobsen and others

2007). A large European double-blind randomised controlled trial is now investigating

whether 3 years grass tablet immunotherapy in 5-12 year olds with grass allergy can prevent

onset of asthma for up to 2 years after stopping treatment (Valovirta and others 2011).

Retrospective studies have suggested that immunotherapy may prevent development of

new sensitisations (Des and others 1997; Pajno and others 2001) although more robust

evidence is required in order to confirm this possibility.

Place in rhinitis therapy.

Allergen immunotherapy within United Kingdom is recommended in patients with a history

of symptoms on allergen exposure and objective confirmation of IgE sensitivity (skin prick

test positive and/or elevated allergen-specific IgE) in the following circumstances:

1. Seasonal pollen induced rhinoconjunctivitis in patients whose symptoms respond

inadequately to usual drug therapy (Evidence level 1++, category A). The choice of SCIT or

SLIT can be based largely on patient preference since the indications are the same and there

are no adequately powered head-to-head comparative trials.

2. Perennial allergic rhinoconjunctivitis in patients with an allergy to cat or house dust mite

who respond inadequately to anti-allergic drugs and where the allergen is not easily avoided

(for example veterinary surgeons and public sector workers). Here the evidence is stronger

for SCIT (Evidence Level 1+, Category A). At present SLIT for house dust mite allergy is not

recommended for routine use.

40


Recent advances

A European Academy of Allergy and Clinical Immunology position paper recommends an

equally weighted combined score of symptoms and use of rescue medication as the primary

outcome in immunotherapy trials (Pfaar and others 2014). A particular problem for

immunotherapy trials for seasonal allergy has been the high variation in pollen counts

within and between seasons. The environmental exposure chamber (Jacobs and others

2012) may provide an alternative solution for dose-finding and as an adjunct, although is

unlikely to replace phase III studies of natural exposure for regulatory approval. WAO has

published standardised reporting systems for systemic reactions to immunotherapy (Cox

and others 2010) and for local reactions (Passalacqua and others 2013a) following

sublingual treatment (‘speaking the same language’) that if implemented could enable more

effective cross-comparisons of adverse events among clinical trials of immunotherapy.

Novel immunotherapy approaches include better standardisation of vaccines by use of

recombinant allergens (Jutel and others 2005; Pauli and others 2008) and their hypo-

allergenic variants (Niederberger and others 2004). Strategies to improve ‘immunogenicity’

whilst reducing the risk of IgE-associated side effects include the development of T cell

peptide vaccines for cat (Couroux and others 2015; Patel and others 2013) and venom

allergy (Muller and others 1998), allergoids (Hoiby and others 2010) (chemically modified

allergens with disrupted tertiary structure) and the combination of allergen with adjuvants

to enhance ‘protective’ immune responses such as immune deviation in favour of Th1

responses (monophosphoryl lipid A (Creticos and others 2006)) or the induction of T

regulatory responses (Toll-like receptor 9 agonist, (DuBuske and others 2011)).

ECONOMIC CONSIDERATIONS WITH REGARDS TO DESENSITISATION

41


In 2013, a Health Technology Assessment of both subcutaneous (SCIT) and sublingual

immunotherapy (SLIT) in patients with seasonal allergic rhinitis undertook detailed cost

analyses recognizing the burden that Allergic Rhinitis places on individuals in the UK and on

the NHS (Meadows and others 2013). Compared to pharmacotherapy, immunotherapy was

cost effective at 6 years after the start of treatment (7 years from an NHS perspective only).

Staff costs and overall productivity losses were greater for SCIT compared to SLIT over the 3

years treatment period, but SCIT was shown to be more cost effective as early as 5 years

after the start of treatment (4 years from an NHS perspective). Pre-seasonal therapy with

SCIT (Pollinex) or SLIT (Oralair), should reduce respective costs further but there remains

uncertainty around their long-term effectiveness of these shorter treatment courses.

Treatment of NAR

Evidence quality from trials is reduced by inadequate patient selection which is often based

solely on negative skin prick tests with or without a history of non-specific triggers such as

smoke, perfume, weather changes. A database search to identify knowledge gaps and

research needs is being compiled by a working party of the American Academy of Asthma,

Allergy and Clinical Immunology and their full report is awaited. Present conclusions, based

on a search of literature from 1960-2010 and using 40% of 2000 articles, (Togias, personal

communication) suggests the following:

Intranasal ipratropium is effective for watery rhinorrhoea (level 1b). (Bonadonna and others

2001) …

Topical capsaicin desensitisation reduced symptoms for several months in NINAR (Blom and

others 1997b; Ciabatti and D'Ascanio 2009; van Rijswijk and others 2003).

42


Topical corticosteroids have an effect in skin prick test negative rhinitis patients (level 1b),

probably on those with underlying inflammation, since studies give variable results (Blom

and others 1997a; Jacobs and others 2009; Lofkvist and Svensson 1976; Lundblad and others

2001; Varricchio and others 2011), and relief was limited in subjects with low levels of nasal

eosinophils in a recent study (Philpot and others 2010).

Topical nasal antihistamines, azelastine and olopatadine (Banov and Lieberman 2001;

Lieberman and others 2011) (level 1b) and a combination of azelastine with fluticasone

(level 111) reduced symptoms in skin prick test negative patients over one year( Price D et

al.J Investig Allergol Clin Immunol 2013; Vol. 23(7): 495-503).

Decongestants and oral antihistamines are ineffective.

Montelukast has not been formally trialled in NAR but low quality studies (Wilson and

others 2001d). Effects of leukotriene receptor antagonist therapy in patients with chronic

rhinosinusitis in a real life rhinology clinic setting suggest a possible effect in SPT negative

patients.

TRPV1 was considered a prime target for neurogenic rhinitis therapy, but a recent study

proved negative when cold dry air challenges were used (Murdoch and others 2014), but did

reduce the response to capsaicin (Holland and others 2014).

Aspirin desensitization

This may be effective in those with aspirin – sensitive NAR, but should be preceded by nasal

or oral aspirin challenge to establish the diagnosis (Fruth and others 2013; Howe and others

2014; Miller and others 2013; Xu and others 2013).

A suggestion for NAR therapy is given in Figure 5.

43


Therapy in NAR depends upon the phenotype. Those with inflammation may respond to

anti-inflammatory therapy, though less well than in AR and higher INS doses and

combinations of therapy may be needed. If these fail a nasal aspirin challenge could be

undertaken, followed by desensitization if positive (Howe and others 2014; Miller and

others 2013). Non inflammatory NAR may respond to anti- cholinergic therapy or to

capsaicin. Some patients require both anti- inflammatory and anti-neurogenic treatments.

Surgery

Surgery is required in only a minority of cases. The indications for surgical intervention are:

1. Drug-resistant inferior turbinate hypertrophy [Poor objective evidence to support

this indication other than in the short term].

2. Anatomical variations of the septum with functional relevance (Passali and others

2003).

There are no well conducted (prospective and randomised) studies supporting the use of

coblation, laser or surgery to the inferior turbinates in patients with rhinitis which

demonstrate benefit, supported by objective measurements, other than in the short term.

Studies of this nature show that surgery to the inferior turbinate does not confer any lasting

benefit (Lavinsky-Wolff and others 2013).

If in future trials of surgery are to be done it would seem that, in the first instance, they

should be limited to patients who have failed to respond to medical treatment given the

evidence that is currently available for the benefit that compliant medical treatment

provides in the majority of patients.

Assessment of Rhinitis Control

44


Since 2001 the ARIA patient classification system for allergic rhinitis has been used in both

clinical and research settings. It focuses on patient symptoms, their time patterns (either

‘intermittent’ or ‘persistent’ and their severity (‘mild’ vs ‘moderate/severe’) and is simple

and quick to administer tool.

In response to a World Health Organisation endorsed trend, disease control rather than

severity is considered a preferable metric to measure and monitor. Three rigorously

developed and validated assessments are available (Control of Allergic Rhinitis and Asthma

Test (CARAT) (Nogueira-Silva and others 2009), Rhinitis Control Assessment Test (RCAT)

(Nathan and others 2010; Schatz and others 2010) and Allergic Rhinitis Control Test (ARCT)

(Demoly and others 2011). More recently the simple and quick MACVIA visual analogue

scale has been developed (reference from GS). To date there has been no head to head

comparison of these tools so it is not possible to rank their utility and validity.

Severe Chronic Upper Airways Disease (SCUAD)

SCUAD is a recently adopted term that defines those patients whose symptoms are

inadequately controlled despite adequate (i.e. effective, safe, and acceptable)

pharmacological treatment based on guidelines. Severe uncontrolled allergic rhinitis, of

whatever aetiology, can be classified as SCUAD which affects 18.5% of allergic rhinitis

patients (Bousquet and others 2009). It is important to differentiate between this situation

and those patients who are symptomatic because they are incorrectly treated or have poor

adherence. The pathophysiology, genotype-phenotype relationships and natural history of

SCUAD are currently poorly understood.

Improving patient adherence in rhinitis

45


Poor adherence is a challenge in the management of allergic and non-allergic rhinitis, just as

it is in other chronic diseases where generic estimates of non-adherence range from 30-60%

and from 50 to 80% for preventive measures (Christensen 2004). There are very few ‘real

life’ studies of adherence in rhinitis to antihistamines and nasal corticosteroids and there

are no data available for adherence with intranasal anticholinergics and cromolyn

(Passalacqua and others 2013b).

Adherence to Specific Immunotherapy (SIT) has been documented in greater detail with

estimates for compliance with subcutaneous (SCIT) regimes ranging from 33-89%, and the

reasons for discontinuation being time taken and annoyance. Sublingual therapy adherence

rates range from 44-97% initially, but discontinuation rates are high with less than 20% of

patients progressing to the third year of therapy. The frequency of follow up visits,

perception of poor efficacy and cost contribute to these high rates of attrition (Passalacqua

and others 2013b).

Unlike some chronic disorders, there has been little effort expended to date in

understanding and improving adherence in rhinitis, however there is evidence to support

the importance of:

Frequent monitoring visits for SLIT. Paediatric patients who were reviewed at three monthly

intervals were significantly more adherent than those reviewed twice or once a year (Vita

and others 2010).

Enhanced patient education. A 3 hour educational program together with written

information achieved greater compliance than standard oral instruction (Incorvaia and

others 2010).

COMPLEMENTARY THERAPY IN ALLERGIC RHINITIS

46


Studies with complementary therapy have used several treatment approaches with view to

treating allergic rhinitis.

Acupuncture

Acupuncture as an intervention for AR has been evaluated in relation to placebo (sham

acupuncture) and medical treatment. Unfortunately robust meta-analysis has not been

possible given the limited number of studies that conform to the trial methodology required

by such reviews, and thus it is not possible to recommend acupuncture as a definite

intervention in AR. Blinding is impossible because of the physical nature of acupuncture.

Studies comparing acupuncture to medical treatment have also focussed on mild AR in that

the intervention has only been an oral antihistamine (Brinkhaus and others 2013; Cao and

others 2014; Hauswald and others 2014). Thus even if these studies show acupuncture

efficacy, the effect is shown in mild AR. The health economics of such intervention must be

considered if a generic second generation antihistamine is as effective. Ear acupressure

studies are limited and weakened further by single blinding, but may be a valuable add on

for patient controlled disease management (Xue and others 2011; Zhang and others 2014).

Recommendation-Grade C

Acupuncture may be considered in mild AR based on patient choice and funding availability.

Herbal therapy

The existing studies are limited and each study focuses on intervention with a specific

herb(s) and there is no available reproducibility of data in repeat studies. Small study

volunteer numbers and lack of robust methodology prevents meta-analysis of such existing

47


studies. It is therefore not possible to recommend a specific herbal product or an overall

herbal therapeutic approach until further studies are undertaken.

Recommendation-Grade D (Not recommended)

Photodynamic therapy

Different light wavelength used in studies have ranged from red light to ultraviolet. Mixed

treatment approaches, limited controlled studies, lack of meta-analysis and of long term

safety data makes it difficult to support such approaches at the current time.

Recommendation-Grade D (Not recommended)

RHINITIS IN PREGNANCY AND DURING BREASTFEEDING

Rhinitis affects at least 20% of pregnancies (Dzieciolowska-Baran and others 2013; Keles

2004) and can start during any gestational week (Dzieciolowska-Baran and others 2013;

Ellegard 2003). Although the pathogenesis is multifactorial, nasal vascular engorgement and

placental growth hormone are likely to be involved (Ellegard 2003; Incaudo 2004). Rhinitis

patients have higher levels of oestrogen and IGF1 during the third trimester. Rhinitis in

pregnancy may not be adequately treated during routine antenatal care, and patients

benefit from a multidisciplinary approach (Soares dos Reis and others 2009). Rhinitis in

pregnancy impacts negatively on quality of life, especially during the third trimester and

women with pre-existing allergic rhinitis are more severely affected (Gilbey and others

2012). Informing the patient that pregnancy-induced rhinitis is a self-limiting condition is

often reassuring.

48


Women developing rhinitis during pregnancy are more likely to deliver female babies

(Indirani and others 2013) and children of mothers developing rhinitis in early pregnancy are

more likely to develop rhinitis themselves (Shinohara and others 2007).

During pregnancy, most medications cross the placenta, and should only be prescribed

when the apparent benefit is greater than the risk to the foetus (Gani and others 2003).

Nasal lavage is safe and effective in pregnant women, reducing the need for antihistamines

(Garavello and others 2010). Chromones have not shown teratogenic effects in animals and

are the safest drug recommended in the first 3 months of pregnancy although they require

multiple daily administrations. The safety of nasal steroids in pregnancy has not been

established through clinical trials. Only minimal amounts of steroid pass into the

bloodstream after using a nasal spray and it is good practice to treat with ‘tried and tested’

drugs (Gani and others 2003). Beclomethasone, fluticasone and budesonide have good

safety records and are widely used in pregnant asthmatic women of these fluticasone has

least systemic bioavailability when used nasally (Demoly and others 2003b; Ellegard and

others 2001; Mazzotta and others 1999). There is considerable clinical experience with

chlorphenamine, loratadine and cetirizine in pregnancy, which may be used in addition, but

decongestants should be avoided (Diav-Citrin and others 2003; Moretti and others 2003).

Patients already on immunotherapy may continue if they have already reached the

maintenance phase but each case must be considered individually. The initiation of

immunotherapy and updosing is contraindicated (Keles 2004).

Similar recommendations can be made about the treatment of allergic rhinitis during

lactation. Nasal lavage is safe to use whilst breastfeeding. Nasal administration of sodium

49


cromoglicate is not known to have any harmful effects when used by breastfeeding

mothers. Antihistamines and nasal steroids should only be used when the clinical imperative

outweighs the potential harm to the child. Antihistamines are excreted in breast milk and,

although not known to be harmful, the manufacturers of most antihistamines advise

avoidance whilst breastfeeding. Chlorpheniramine may cause drowsiness and poor feeding

in the baby. Both loratidine (Hilbert and others 1988) and cetirizine appear safer with low

levels found in breast milk (Briggs and others 2001). The lowest dose should be used for the

shortest duration.

RHINITIS IN CHILDREN

Rhinitis is a common presentation in children and there are several underlying causes.

Acute infectious rhinitis is frequent, particularly in young children, and generally

does not require medical attention.

Chronic infectious rhinitis (rhinosinusitis), particularly if severe, can be a

manifestation of underlining pathologies such as Primary Ciliary Dyskinesia, Cystic

Fibrosis, and Immunodeficiency.

Retained foreign body, nasal septum deviation, unilateral choanal atresia, cerebro-

spinal fluid leak, and nasal polyposis can present with rhinitis.

Allergic rhinitis is the focus for allergy specialists and paediatricians:

o It has a significant impact on children’s quality of life and can have a

detrimental effect on sleep, behaviour, school performance and family

dynamics (Walker and others 2007)

o Its presentation in children can be atypical and it is influenced by the

associated co-morbidities in the different age groups, as summarised in the

50


recently published EAACI Paediatric Rhinitis Position Paper (Roberts and

others 2013) (figures x and z- reproduced with permission). The same

document gives guidance on how to recognize its comorbidities (Figure z –

reproduced with permission).

o It can present in association with other atopic disorders and it is often

associated with asthma, atopic dermatitis and food allergy.

o In children as in adults the link between rhinitis and asthma has been

demonstrated by several studies.

Otitis media with effusion and/or adenoidal hypertrophy have been reported as associated pathologies in younger patients; the mechanisms underlining this link have however yet to be fully elucidated. Some studies suggest benefit to these common paediatric conditions from rhinitis treatment (Scadding G1. Non-surgical treatment of adenoidal hypertrophy: the role of treating IgE-mediated inflammation. Pediatr Allergy Immunol. 2010 Dec;21(8):1095-106. doi: 10.1111/j.1399-3038.2010.01012.x.

Scadding and others 2014) (3,4,5). Ask Pina for these refs, include Scadding one on OME pub

2014= Glenis K. Scadding, Kaukau Rajput, Susan Hills, Yvonne Darby, Anna Jansz, David

Richards*, Helen Tate+ and Simon Gane

Double-blind, placebo controlled randomised trial of medical therapy in

otitis media with effusion.

o

o The approach to diagnosis in children is similar to that in adults: history, skin

prick test and anterior rhinoscopy. Component resolved diagnosis (CRD) may

be helpful in selected patients when allergen specific immunotherapy is being

51

http://www.ncbi.nlm.nih.gov/pubmed/?term=Scadding+G+and+adenoid

http://www.ncbi.nlm.nih.gov/pubmed/?term=Scadding%20G%5BAuthor%5D&cauthor=true&cauthor_uid=20609137


considered and the seasonal symptoms are not clear (Stringari and others

2014).

o Entopy (local allergic rhinitis) is found in this age group ( level D) (Forester

and Calabria 2010; Payne and others 2011).

o Therapy of rhinitis in children is based on the same principles as in adults,

however it should take into account specific paediatric needs, such as

acceptability, practicality for both children and parents, and concern for

potential side effects.

o Nasal saline irrigation is effective in the treatment of AR in children (Chen and

others 2014; Garavello and others 2003).

o Brief concomitant use (3 days) of topical decongestants can be helpful in

children with significant nasal blockage to aid introduction of topical nasal

steroid therapy.

o Recommendation for continuous use of intranasal steroids can often create

anxiety in parents; Intranasal steroids with low bio-availability have a better

safety profile at recommended doses and should be used in preference

(Figure 4) (Allen and others 2002a; Schenkel and others 2000).

o It is advisable to monitor growth in children, especially if they are receiving

steroids by multiple routes (Allen and others 2002b) (see also table 7).

o A short course (3 to 7 days) of oral corticosteroids may be required in severe

cases. Intramuscular steroids have no role in the treatment of AR.

o Immunotherapy is recommended mostly for difficult to treat subjects who

have failed maximal pharmacotherapy; the potential added benefit in disease

52


prevention should be considered when treating children (Moller and others

2002; Niggemann and others 2006).

o Education on therapy plays an important role on treatment outcome and

both children and carers should be provided with the relevant information

and appropriate training (Indradat and others 2014).

Quality of Life Questionnaires for rhinitis

The burden of rhinitis for an individual patient can be estimated using Patient-Reported

Outcome Measures (PROMs). Generic PROMs such as the EQ-5D allow a comparison

between different diseases and are particularly useful when calculating the incremental

cost of new treatments. However, a disease-specific validated Quality of life (QoL)

questionnaire is more sensitive when assessing severity of disease and response to

treatment. In routine clinical practice the use of such tools allows greater focus on

symptoms important to the patient. Commonly used and validated quality of life disease

specific scoring systems include the RQLQ for allergic rhinitis and rhino-conjunctivitis,

the SNOT-22 or RSOM-31in chronic rhinosinusitis and a modified SNOT-16 in acute

rhinosinusitis.

FUTURE RESEARCH

AR

Prevention of AR development

Adoption of single scheme for assessing control

Prevention of progression from AR to asthma: confirmation of effect of immunotherapy,

investigation of AR well-controlled by pharmacotherapy.

53


Reduction of proportion of SCUAD sufferers

NAR

Prevalence- accurate figures needed.

Endotypes

Trials of therapy in well – selected endotypes

Acknowledgements

PATIENT INFORMATION LEAFLET

Rhinitis means inflammation of the lining of the nose. Rhinitis is defined clinically as

symptoms of runny nose itching, sneezing and nasal blockage (congestion). Common causes

of rhinitis are allergies which may be seasonal (‘hayfever’) or occur all-year-round (examples

include allergy to house dust mite, cats, dogs and moulds).Infections which may be acute or

chronic represent another common cause. Rhinitis (whether due to allergic or other causes)

is a risk factor for the development of asthma. Rhinitis is also implicated in otitis media with

effusion (glue ear) and in sinusitis which should rightly be termed rhinosinusitis since sinus

inflammation almost always involves the nasal passages as well.

Allergic rhinitis is very common, affecting one in four in the UK. As with other allergic

disorders (asthma, atopic dermatitis) rhinitis is much more common in westernized

societies; the prevalence of rhinitis continues to rise in many countries.

54


People with a family history of allergy are more likely to get allergic rhinitis. No method has

been found to prevent it developing. Allergic rhinitis may itself be the first manifestation of

allergic disease, e.g. as hay fever in teenagers or adults. Further allergies can occur- to things

like house dust mites, pet allergens. Rhinitis may progress to persistent symptoms with

resultant nasal congestion which impacts on adjacent structures such as the sinuses, throat,

middle ear and bronchial tubes.

It can be very mild, moderate or severe.Allergic rhinitis is frequently ignored or regarded as

trivial by family members, doctors and even sufferers themselves, probably because

recurrent colds are common, particularly in small children. This is a big mistake since not

only does rhinitis reduce quality of life, it can impair sleep and reduce school performance

and attendance at work. Allergic children have been shown to have more infections and

more problems with those infections.

Asthmatic children who get colds are 20 times more likely to be hospitalised due to their

asthma if they are allergic and if they are exposed to high levels of their provoking allergens.

Adequate treatment of underlying allergic disease helps to diminish these problems.

Diagnosis rests on taking an adequate detailed history and supplementing this by

examination and, if necessary, specific allergy tests. The timing of symptoms in relation to

possible allergen exposure is of primary relevance.

Treatment of Allergic Rhinitis

This falls into 4 categories:

1. Allergen and irritant avoidance. Rhinitis is usually caused by inhalant allergens and very

55


rarely by food. Some allergens such as pets can be avoided; others such as pollens are more

difficult- although a holiday abroad or by the sea at the height of the relevant season can

help. House dust mites are hard to avoid sufficiently reducing symptoms but some patients

do find benefit from allergen proof bed covers particularly if such measures are combined

with rigorous cleaning, avoidance where possible of soft furnishings and heavy curtains and

use of hard flooring. However, in controlled clinical trials, such mite avoidance measures are

not of proven value at the present time. Avoidance of irritants such as smoke also helps to

reduce symptoms. Simply washing out the nose with a salt water solution can be very

soothing. This can be achieved with half teaspoon of salt, half teaspoon of bicarbonate of

soda (baking powder) added to a pint of lukewarm water, with gentle sniffing of the solution

from the palm of the hand. Also salt sprays and custom-designed salt douches are

inexpensive and available from high street chemists.

2. Drug therapy. Mild-moderate hay fever responds to antihistamines but it is very

important to take advice from pharmacists and choose non-sedating antihistamines,

otherwise driving, work and school performance is very likely to be impaired even in people

who do not feel drowsy and who are not obviously sleepy. More problematic and persistent

rhinitis is better treated with a topical nasal corticosteroid administered by spray or, in the

case of associated sinusitis and/or nasal polyps by use of corticosteroid nasal drops. The

new nasal corticosteroid sprays are not absorbed and can be very safely be used in adults

and children.

Avoidance of directing the spray towards the nasal septum (the partition in the middle of

56


the nose) and use of the nasal device without fiercely sniffing the spray into the back of the

throat provides optimal benefit.(FIGURE X) Symptom relief is not immediate and treatment

may take several days or a week or two to be fully effective. Combinations of treatments

may be needed – intranasal antihistamine plus intranasal corticosteroid is better than either

alone in reducing all symptoms.Other potentially useful treatments include anti-leukotriene

tablets (Singulair), chromones (Intal, Nedocromil) and ipratropium (Rhinatec).

3. Immunotherapy (desensitization). Immunotherapy involves giving graded increases of

allergens to which the sufferer is sensitive in order to induce allergen tolerance, which may

last for years following discontinuation. Immunotherapy is reserved for patients with one or

two major problematic allergens and without chronic asthma who are not controlled by the

above measures. Injection (subcutaneous) or under the tongue (sublingual) immunotherapy

is usually given regularly over 3 years. This form of treatment must only be prescribed

initially by specialists in allergy.

Sublingual immunotherapy once the first dose has been given under expert supervision can

be administered each day in the home. Sublingual reactions are very mild- mostly involving

local itching and swelling in the mouth and throat- and short term lasting 1-2 weeks or less.

Local side effects are to be expected and usually apparent at the first dose which should be

given under supervision. Side effects from injection immunotherapy may occasionally be

more severe so injections must take place in the presence of a trained physician in a setting

where immediate resuscitation facilities are available. Pre-seasonal treatment is effective

57


for seasonal allergies, but it is not yet clear whether pre-seasonal use confers long term

benefit, as observed for the injection route when used regularly all year round for 3 years.

4. Surgery. Surgery is only very rarely needed for rhinitis. Occasionally surgery with/without

turbinate reduction is needed to allow access to the nose for more effective use of sprays or

to open the sinuses in patients insufficiently responsive to medical treatment because of

structural problems.

Progress of disease

Once present inhalant allergen sensitivity tends to remain in many, but not all, patients.

Some individuals lose their hay fever and their allergies do not progress.

It is worth making your friends and family aware of your allergies so that you do not suffer

from major exposure- such as a house with cats, or a very dusty bedroom.

Contact - ??Allergy UK

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LEGENDS TO TABLES and FIGURES

Table 1. Allergic triggers for rhinitis.Many inhalant allergens cause rhinitis symptoms- but occupational ( Table 6 ) and non- allergenic triggers( Table 3 ) should also be considered when taking the history.Table 2 Infectious causes of rhinitis.Table 3 Triggers for non – allergic rhinitisTable 4. Aetiology and Associations of Allergic Rhinitis

Table 5.Co- morbidities of Allergic Rhinitis.

Some co- morbidities appear as consequences of AR, e.g. concentration and sleep problems, others co- exist with it as a consequence of underlying allergy, eg atopic dermatitis .The mechanism of the association between asthma and rhinitis is uncertain, but the tendency for asthma to succeed rhinitis, the demonstration that nasal allergen challenge in AR gives lower respiratory tract inflammation and the prevention of progression of AR to asthma by allergen immunotherapy suggest that the asthma is consequential in individuals in whom rhinitis is the initial manifestation of atopic disease. Table 6.Occupational Rhinitis triggersTable 7.Allergen Avoidance measuresTable 8.Effects of medication upon individual rhinitis symptomsTable 9.Oral antihistamines.Table 10. Summary of SCIT and SLIT

Figure1. Modified ARIA Classification of Rhinitis NB THE FIGURE NEEDS THE PREVIOUS VERSION_ IN WHICH SEASONAL AND PERENNIAL IS ADDED AT THE BOTTOM

In the UK, where seasons are clear, an additional subdivision into seasonal and perennial is helpful, in diagnosis and in therapy, particularly allergen avoidance and immunotherapy.

Figure 2.Immunological mechanisms of Allergic Rhinitis Figure 3. AR Treatment algorithm.

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Additional therapies can be accomplished using two different medications, or a combination treatment in one device. There is , as yet , no comparative evidence on which to base this choice, however concordance appears more likely when the regime is simple. Figure 4. Bioavailability of intranasal corticosteroids. The more recent molecules have little systemic uptake and are suitable for use in children and for long term therapy(.Grade A evidence) Figure 5.Treatment of Non- Allergic Rhinitis.The division into those with and without nasal inflammation can be made on the basis of nasal smears, and possibly on nasal NO levels, though this latter is not certain .Patients who fail on therapy can be tried on a combination of BOTH ANTI- INFLAMMATORY PLUS ANTI – NEUROGENIC TREATMENT,( Grade D evidence)Figure 6. How to Use a Nasal Spray. Evidence grade D.Figure 7. Rhinitis in Children.With permission from EAACI.Figure 8.Recognition of Rhinitis in Children at different Ages.With permission from EAACI.

? add Figure 9.Treatment of Rhinitis in ChildrenWith permission from EAACI

Appendices

A1Levels of EvidenceA2.Grades of RecommendationA3.Combination therapy for Rhinitis.A4.Management of Non- Allergic Rhinitis.Trials of level 2+ , involving exclusion of patients with allergen specific IgE or a response to nasal corticosteroids , have been included

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Table 1. Allergic triggers for rhinitis

Trigger types Origin/specific example of trigger

Type of rhinitis caused

Mites House dust mite, storage mites, allergen in mite faecal pellets

Major causes of perennial rhinitis

Pollens Trees, grasses, shrubs, weeds Main causes of seasonal rhinitis; cross-reactivity among pollens

Animals Cats, dogs, horsesMice, rats

Allergen in sebaceous glands & salivaAllergen mainly in urine

Fungi (Moulds) Alternaria, Cladosporium, Aspergillus

Seasonal and/or perennial symptoms

Occupational-induced(see also table 2)

Occupation-Aggravated

Flour, latex, laboratory animals, wood dust, enzymes, other airborne proteins

Smoke, cold air, formaldehyde, sulphur dioxide, ammonia, glues, solvents, etc. (Drake-Lee and others 2002; Shusterman 2003)

Reversible with early diagnosis and avoidance but becomes chronic and irreversible if exposure is prolonged (Petrick and Slavin 2003).May progress to asthma. Diagnosis based on symptom diary cards and provocation tests (table 3).

Pre-existing rhinitis can be aggravated by work-place irritants

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Table 2 Infective causes of rhinitis

Infective agent type Examples of infective agent

Caused disease pattern

Viruses Common cold viruses, e.g. rhinovirus, coronaviruses, RSV, etc.

Sinus changes on CT scan remain for up to 6 weeks after the infection (Gwaltney 2002).0.5-2% become superinfected by bacteria (Gwaltney, Jr. 1999). “Colds” may exacerbate asthma and COPD (Hurst and others 2005; Johnston and others 1995).Children average 6-8 “colds” per year (Ramadan 2005).

Bacteria Streptococcus, Haemophilus, Moraxella, Staphylococcus, Mycobacteria

Acute infection causes nasal obstruction, facial pain, crusting, purulent discharge.Can progress to rhinosinusitis

Fungi and other opportunistic infections

Aspergillus Rarely cause symptoms; mainly affect immuno-suppressed individuals (Fokkens and others 2005).

Protozoa Leishmania Chronic indolent disease with granulomatous changes and destruction

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Table 3 Types and possible triggers of non-allergic rhinitis

Type Suggested triggers/cause Signs/symptomsEosinophilic or NARES (non allergic rhinitis with eosinophilia syndrome)

50% develop aspirin sensitive disease with asthma and nasal polyposis later in life (Leone and others 1997)

Skin tests negative but nasal smears show eosinophilia. Perennial symptoms with paroxysmal episodes. About 50% have bronchial hyper-reactivity (Leone and others 1997).

Autonomic (vasomotor)

Triggered by physical/chemical agents

More common in middle age with clear rhinorrhoea especially in the morning. Less favourable course than allergic. Possibly caused by parasympathetic hyperactivity (Garay 2004).

Drugs -adrenergic blockers, ACE inhibitors, chlorpromazineCocaine

Nasal decongestants (with prolonged use)Aspirin/NSAIDs

Nasal blockage

Rhinorrhoea, crusting, pain and nasal septum perforation reduced olfaction (Yewell and others 2002)Rhinitis medicamentosa with chronic nasal blockage (Tan and Corren 1995)Acute rhinitis symptoms +/- asthma

Hormonal Pregnancy (Canonica and Passalacqua 2003), puberty, HRT, contraceptive pill (Drake-Lee and others 2002; Shusterman 2003). Possibly hypothyroidism, acromegaly (Cullinan and others 1999; Petrick and Slavin 2003)

All can cause nasal blockage and/or rhinorrhoea

Food Alcohol, spicy foods, pepper, sulphites

Rhinorrhoea, facial flushingGustatory rhinorrhoea

Atrophic Klebsiella Ozonae (Gautrin and others 2001b) or secondary to trauma, surgery, radiation

Foul-smelling odour, crusting, hyposmia, nasal blockage (Gautrin and others 2001a)

Primary mucus defect Cystic fibrosis Children with polyps must be screened for cystic fibrosis (Cartier and others 1984)

Primary ciliary dyskinesias

Kartagener and Young syndromes

Rhinosinusitis, bronchiectasis and reduced fertility.

Systemic/Inflammatory Sjogren, SLE, rheumatoid arthritis,Churg-Strauss (Houba and others 1998)

Nasal blockagePolyps, sinusitis, asthma, eosinophilia

Immunodeficiency Antibody deficiency Chronic infective sinusitisMalignancy Lymphoma, melanoma,

squamous cell carcinomaBloody, purulent discharge, pain and nasal blockage – symptoms may be unilateral

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Granulomatous diseases

SarcoidosisWegener’s disease [274]

External nasal swelling or collapse, sinusitis, swelling, crusting, bleeding, septal perforation

Structural abnormalities

Nasal septal deviation Unilateral nasal obstruction unlikely to present unless additional cause, e.g. rhinitis

Idiopathic Unknown cause – Diagnosis of exclusion

May respond to topical capsaicin (Gwaltney 2002; Johnston and others 1995; Wernfors and others 1986)

Local AR Allergens as for AR (see table 1) Skin test negative, but positive response to nasal allergen challenge. The prevalence is up to 25% in Spain, there are only estimates in the UK.

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Table 4: Aetiology and associations of AR

Factor Comments Evidence level References

Non-modifiable factors

Genetics/family history of atopy

Hay fever: 60.3% concordance in MZ twins, 31.5% in DZ twins.

74-90% interindividual liability to AR accounted for by genetic factors.

Family history of atopy greatest risk factor for atopy and atopic disease in children.

1765 twin pairs, questionnaire only

8,633 5-year-old twin pairs, questionnaire only

Prospective birth cohort, 1,218 children followed up at age 4, cord blood IgE at birth

Rasanen, Allergy, 1998

van Beijsterveldt, ERJ, 2007

Tariq, JACI, 1998

FLG null mutations Presence of null mutations in the gene coding for the epithelial structural protein filaggrin are associated with AR, including in the absence of atopic eczema.

Systematic review and meta-analysis

Van den Oord, BMJ, 2009

Personal history of atopy

Positive skin tests to aeroallergens at baseline risk factor for incident AR in childhood and adolescence.

Eczema in 1st year of life risk factor for childhood AR.

Prospective, case-control, cohort, and birth cohort studies.

Codispoti, JACI, 2010; Ulrik, Allergy 2010; Westman, JACI, 2012; Alm, Paed All Imm, 2011; Kellberger, JACI, 2012; Schafer, Allergy, 2007.

Male sex pre-adolescence

Female sex post-adolescence

Greater risk of childhood AR

Greater risk of adult-onset AR

Prospective, longitudinal, cohort studies

Alm, Paed All Imm, 2011

Kellberger, JACI, 2012

Early life factors

Gestational age at birth Prematurity may be Cases (preterm, 166) Siltanen, JACI, 2011

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protective against adult atopy and AR (assessed by prescriptions for anti-histamines and intra-nasal corticosteroids

vs control (term, 172) study

Birth cohort study, 630,090, AR assessed by prescription rates.

Crump, JACI, 2011

Birth by caesarean section

Positive association with atopy and AR in school age in children with family history of atopy

‘At risk’ birth cohort (432, family history of atopy) followed to age 9

Pistiner, JACI, 2008

Family size and birth order

AR risk decreases with increasing number of siblings; effect more marked for presence of younger siblings

Finding repeated in several large cohorts

Strachan, BMJ, 1989; Braback, Clin Exp All, 1998; Colispoti, JACI, 2010

Early day care attendance

Children without siblings but attending day care have reduced risk of AR than those not attending day care; early day care attendance protective against atopy

Retrospective questionnaire data from European Community Respiratory

Health Survey; cross-sectional questionnaire and SPT/serum sIgE

Svanes, Thorax, 2002

Kramer, Lancet, 1999

Infectious disease markers

Serologic evidence of acquisition of Hepatitis A, T. gondii, HSV 1 associated with reduced frequency of AR; Hep A antibody positivity inversely correlated with SPT positivity

33, 994 individuals studied as part of US National Health and Nutrition Examination Survey; questionnaire, SPT and serological data.

Matricardi, JACI, 2002

Rural/farming environment

Growing up in rural environment, versus urban, appears to be protective, particularly farm animal exposure and exposure to unpasteurised milk before 1 year of age

Reproducible finding in several large observational studies

Braback, Clin Exp All, 2004; Eriksson, Allergy, 2010; Loss, JACI, 2011; Sozanska, Allergy, 2013; Riedler, Lancet, 2001

Breastfeeding Breastfeeding ever versus none not

ISAAC phase 3 Bjorksten, Allergol Immunopathol, 2011

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associated with altered risk of AR, but decreased risk of severe AR.

Absence of exclusive breastfeeding for 2 or more months associated with increased AR incidence in late adolescence

Breastfeeding retrospectively assessed at age 9-11, but effect on AR assessed prospectively at age 15-18

Kellberger, JACI, 2012

Weaning Greater food diversity at 6 and 12 months associated with less AR at age 5; early introduction of fish may be protective

Prospective, birth cohort, 3,142 children, HLA-limited; prospective, longitudinal cohort, 8,176 families

Nwaru, JACI, 2014; Nwaru, JACI, 2013; Alm, Paed All Imm, 2011

Anthroposophic lifestyle, paracetamol and antibiotic use

Use of paracetamol and antibiotics in early life associated with increased risk of AR at age 6-7.

ISAAC phase 3 studies Beasley, Lancet, 2008; Foliaki, JACI, 2009

Steiner school children have reduced incidence of AR ages 5-13

Cross-sectional, controlled study, questionnaire, SPT, sIgE, clinical examination

Alm, Lancet, 1999

Pet exposure Conflicting data: exposure to a cat or dog in the first year of life may be protective for AR at age 7-9 and for cat SPT positivity at 12-13.

Cross-sectional, questionnaire study at two time points, SPT in a subset

Hesselmar, Clin Exp All, 1999

Early exposure to cat a risk factor for AR in 6-7 year olds

ISAAC phase 3 study Brunekreef, Epidemiology, 2012

Other associations

Smoking Variable data: smoking not associated with increased risk of AR, but may increase risk of NAR; second hand smoke exposure may

Large cohort studies

Systematic review and meta-analysis

Eriksson, Clin Resp J, 2012; Eriksson, Allergy, 2013

Saulyte, PLOS medicine, 2014

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have modest association with AR, including in children; smoking may increase risk of house dust mite sensitisation, but reduce risk of pollen sensitisation

ECRHS analysis

Jarvis, JACI, 1999

Vitamin D Variable data: Low serum vit D associated with AR in men

Prospective study, vit D at baseline, incident AR at follow up

Mai, Allergy, 2014

Maternal vit D intake in pregnancy inversely associated with AR aged 5

Retrospective diet questionnaire after delivery, follow up of child at 5 years, HLA-limited

Erkkola, Clin Exp All, 2009

Serum vit D level positively correlated with AR in adults

18,224 individuals in NHANES 3

Wjst, Allergy, 2007

Traffic-related air pollution

No definitive demonstration of an association with AR or allergic sensitisation

Pooled analysis of 6 birth cohorts

Meta-analysis of European birth cohorts

Fuertes, JACI, 2013

Gruzieva, JACI, 2014

Housing High indoor humidity and poor ventilation risk factors

Visible damp (self-reported) associated with rhinitis; higher measured humidity associated with greater Der p 1 levels in mattresses

Retrospective questionnaire study, 2,481 7-9 year olds

ISAAC phase 2, 46,051 children

Aberg, Allergy, 1996

Weinmayr, Clin Exp All, 2013

Diet Consumption of fast food 3 or more times per week associated with AR in 6-7 year olds and adolescents; fruit consumption has opposite effect

ISAAC phase 3 study Ellwood, Thorax, 2013

Lifestyle/physical activity

Paradoxical data: Weak positive association with hours spent TV-viewing and

ISAAC phase 3 study Mitchell, Clin Exp All, 2013

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AR, but also between vigorous physical activity and AR in 13-14 year olds

Alcohol consumption Level of alcohol consumption positively correlates with development of AR in women

Prospective study, 5,870 Danish women, free from AR at baseline

Bendtsen, Clin Exp All, 2008

Climate change Warmer climate may lead to longer pollination seasons and greater geographical distribution of allergenic flora and fungal species

Retrospective analysis: correlation between minimum spring temperature, tree pollen counts, and number of patients visiting an outpatient clinic for AR

Kim, BMC Public Health, 2011

Occupation Occupations with highest risk of developing occupational asthma include bakers, furriers, veterinarians, livestock workers

Finnish Register of Occupational Diseases

Hytonen, Int Arch Occup Environ Health, 1997

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Table 5 Co-morbid associations with rhinitis

Conjunctivitis :PL ADD CANONICA GW paperAuthors Study No patients Age yrs Aim of the study ResultsBozkurt MK et al 2010

Prospective ENT examination in children with vernal keratoconjunctivitis (VKC)

26 males1 female

12+/-4.4 AR prevalence in children with VKC

37% of children with VKC suffer from AR.Median IgE in AR +ve was 262.5Ku/L vs 40.2 in non- ARPatients with VKC should see an ophthalmologistand an allergist

Ibanez MD et al 2010

Multicentre study

1275 recruited from271 centres

6-12 AR (60.7% seasonal and 39.3% perennial) conjunctivitis co-morbidities

Persistent/Severe AR has > co-morbidities .The most frequent is conjunctivitis (53%)

Bertelsen RJ et al 2010

Parental interviews of 1019 cohort

254 with rhinitis (=25%)

children Prevalence of rhinitis co-morbidities

87.4% had at least one rhinitis co-morbidity .Conjunctivitis was present in75.6% (11.8% of them also had asthma & eczema)

Kim Hy et al 2013

ISAACQuestionnaire(12 months evaluation)

615 3-6 Prevalence of rhinitis in children with conjunctivitisand conjunctivitis in children with rhinitis

Prevalence of rhinitis in children with conjunctivitis was 64.8%Prevalence of conjunctivitis in children with rhinitis was 23.6%

OME/Hearing abnormalities: suggest Rita adds add Umapathy D & Scadding GK A community based questionnaire study on the association between symptoms suggestive of otitis media with effusion, rhinitis and asthma in primary school children.Umapathy D, Alles R, Scadding GK.Int J Pediatr Otorhinolaryngol. 2007 May;71(5):705-12. Epub 2007 Mar 1.


Multi centre prospective

1275271 centres

6-12 Evaluation of ear co-morbidities in AR

23.8% of AR had OME;17.3% of AR had adenoidal hypertrophy

Singh SJ et al 2011

Prospective 30patients 20controls

Adults Audiological and ontological status in AR

All patients had sensorineural hearing loss>high frequency& otoacustic emission abnormalities

90

http://www.ncbi.nlm.nih.gov/pubmed/17335912




Bozkurt MK et al 2010

Prospective 26 males1 female

12.1+/-4.4 Prevalence of Eustachian tube dysfunction (ETD) in VKC and AR

Patients with AR and VKC are 3x> to have abnormal tympanograms and suffer from ETD than control

Depression/ADHD/ Altered sleeping patterns/anxiety in familiesChen MH et al 2013

NationwideProspective

1673 12-15 AssociationAR and depression after 10years FU

Severe depression 2.5%vs 1.2%Any other depression 4.9% vs 2.8%

Tsai MC et al 2011

Nationwide on Taiwan National Health Research Database

226550 <18 Prevalence & risk of ADH in AR children

Increased ADH rate P<0.001(eczema & asthma do not carry the same risk

Kalpakliogh AF 2009 et al

Observational study on sleeping symptoms

48 Adults Prevalence of OSA in AR vs NAR

OSA 36% in AR vs 83% in NAR (OSA OR in NAR 6.4).AR& NAR were snorers

Emin O 2009 et al

Prospective 82 vs 70 mothers of AR

7-15 Anxiety parameters scores in mothers of AR children vs controls

Anxiety scores significantly > in mothers with AR childrenP<0.02

Lavigne F 2011

Prospective for 12/weeks

34 AR21 NAR

Adults Effects of mometasone on sleep parameters & upper airway inflammation on biopsies

Significant improvement on sleeping parameters &reduction of eosin in AR only

Messias E et al 2010

National co-morbidity survey

5692 Adults Associationbetween seasonal allergies and suicide ideation

Significant association (OR 1.27);not with suicide attempts

Vuurman EFPM et al 2014

Double blind randomized cross-over following nasal provocation with pollen extract and during the season

19 (9 females/10men)

Adults Effect of untreated AR on driving performance compared with treated AR

Magnitude of impairment (evaluated on standard deviation of lateral position of performance) comparable to that seen driving with 0.03% alcohol. Rx with anti H1 or steroids reduces the effects on driving perfomance

Rhinosinusitis/anosmia

91



Multi centre prospective

1275271 centres

Children Co-morbidities in children with AR

26.1%of AR had rhinosinusitis

Guss J et al 2009

Prospective 51 (80% allergic)

Adults Investigate the olfactory function in AR (with Smell Identification Test and also CT scan)

50% of AR with normal CT scored in the 30th percentile on olfactory test . 50% of allergic patients had hyposmia

Asthma:Rita needs to add Shaaban, Lancet , ECHRS stud;Leynaert paper; Settipane papers and Magnan one.Ciprandi G et al 2011

Prospective 89 AR940 controls

Adults Follow up of patients with AR every 2 years for 8years to investigate spirometric abnormalities /BHR

34/89 AR patients develop BHR after 8years

Sensitization for mite, birch, parietaria as well as rhinitis duration are risk factors

Yiamaz o et al 2014

Prospective 57 Children with asthma ex’ion

Evaluate the risk factors for recovery of lung function tests after moderate/severe asthma exacerbation

AR is a significant factor affecting the recovery time of pulmonary function tests and impacts asthma management


Prospective multicentre

1275 ChildrenFrom 271 centres

Evaluation of comorbidities for AR in a Spanish population

49.5% co-morbidity with asthma: allergy is a systemic disease

Navarro A et al2008

EpidemiologicprospectiveMulti centre

942with asthma

Mean age 35.563% female

Investigate the link between the upper and lower airways

89.5% had ARCorrelation between severity of rhinitis and asthma (P<0001) & inverse correlation with the age (P<0.0001) and severity of asthma (P<0.05)

De Andrade CR et al 2008

Cross sectional study using ISAAC questionnaire

3083 students(47.3% males)

13-14 Evaluation of Asthma and AR co-morbidity

comorbidity asthma and rhinitis symptoms was 8.4%Among asthmatic adolescents, AR symptomswere reported in 46.5%

Ko FW et al 2010

Cross sectionalon questionnaire

600 (with asthma)

267male333 female

Evaluation of prevalence of AR in asthma

77% of asthmatic had rhinitis in the past 12 months (of whom 96% were previously diagnosed with AR)Patients with asthma and rhinitis: nasal steroid usage (49%) had < ED visits 13vs25%) and <hospitalization for asthma (5%vs 13%)

Erikson J 2011 Postal Questionnaireon respiratory health

18087(62% responded)

Adults Evaluation between rhinitis phenotypes and symptoms presentation and risk factor patterns in asthma

Prevalence of asthma in AR was 19.8%Prevalence of AR in asthma was 63.9%Asthma with chronic rhinitis had>asthma symptoms and bronchitis (P<0.01)

92


FH of allergy has a >OR for asthma and AR than for asthma and CRS

Bertelasan R Parental interviews

254 Childrenwith rhinitis

Evaluation of co morbidities of rhinitis

87.4% had at least one allergy related co-morbidityChildren with rhinitis and allergic sensitization (72.8%) had>BHR, severe BHR (7.5% vs 5.8%) and conjuntivitis

Valero A et al 2009

Cross sectional international population study based on questionnaire

3225 (one +ve skin test )

10-5053% Male

Evaluation on the link between AR, asthma and skin test sensitization

Asthma was present in 49% of ARAsthma severity was associated with longer time since the onset and allergic rhinitis severity.Patients with asthma have higher number of allergen sensitization and sensitization intensity than those without asthma (P<0.01)

Kin HY et al 2013

Cross sectionalStudy using ISAAC questionnaire

615 Children (306)

Evaluation of allergic co-morbidities in pre-school children

Prevalence of AR in children with asthma was 64.3%Prevalence of asthma in children with R was 21.6%

Oral allergy syndrome/food pollen syndrome/food allergyWestman M et al2012

Prospective 2024 Children IgE tested (inhalants) at 4 and 8years

Natural course of AR and co-morbidities in children

Increase AR from 5% to 14% from 4 to 8years; decrease of NAR from 8% to 6%.4yrs sensitized but not allergic had AR at 8years in 56% of cases

25% of 8yrs with AR has also OASCaliskanerZ et al 2010

Prospective 11178 men 33 women

Adults Clinical parameters comparison between AR with OAS and without

OAS > in women (P=0.01) (OR M/F3.80).OAS relates to nasal itching (P<0.05).OAS >IgE (ns)Regression analysis:association with asthma, age and severity of nasal symptom score

Sahin-Yilmaz A et al 2010

Retrospective 283 Peanut, shrimp and milk IgE and rhinitis

23.4% peanut IgE +ve and 22.2% IgE+ shrimp in inhalant +patientsPeanut and shrimp were the >common sensitivities in rhinitis patients

Laryngeal symptoms

93


Vargut MM L 2011 et al

Observational prospective

6control6 AR adult singers

4 females2men

Effects of nasal provocation with pollen extracts and during the HF on Laryngeal parameters

Rapid induction of laryngeal irritation/ globus (no objective laryngeal changes on provocation and during the season)

Rhinitis/atopic disease and migraineMunoz-Jareno N et al et al 2011

Retrospective study FU for 6months

216 5-15 Prevalence of atopy in children with migraine

Prevalence of rhinoconjunctivitis, asthma and atopic dermatitis are statistically significant in children with migraine (OR 7.3; P<0.01for rhinoconjunctivitis;OR 4.69:P<0.01 for asthma; OR 7.1; P< 0.01 for atopic dermatitis

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Table 6 Common causes of occupational rhinitisAgents High MW Low MW Occupation/Industry

Animal proteins Mouse, rat, guinea pig, crabs, etc. urinary and epithelial proteins

Laboratory research, animal breeding [207-209], crab processing industry [210]

Vegetable proteins

Wheat and other cereal flours and grains, latex [51]

Baking [211], milling, food processing,hospital workers

Enzymes Protease, amylase, cellulase, lipase

Food processing, detergent manufacture, pharmaceuticals

Pharmaceuticals Antibiotics, morphine, cimetidine

Pharmaceutical manufacture and dispensing

Chemicals Diisocyanates, colophony fumes, (trimellitic) acid anhydrides (TMA) [212], cyanoacrylates, epoxy resins, alkyd/polyunsatu-rated polyester resins [213] Persulphate Salts, Plicatic Acid (Hox)

Spray painting, Electronic soldering, Plastics and paint manufacture, vinyl flooring, resin production. Cleaners. HairdressersCarpentry and Furniture Making

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Table 7 Recommendations on the use of single measures on HDM avoidance

Measures used individually

Grade of

recommendation

Encase mattress and pillows in plastic or special allergen proof fabric D*

Hot wash bedding at 55ºC and damp wipe mite proof covers every 1-2 weeks D

Remove carpets and replace with hard wood floor D

Use of acaricides on carpets and soft furnishing D B

Minimise objects that accumulate dust D

Remove soft toys from the bed as they harbour high levels of Der p1 D

Remove upholstered furniture and replace with leather, plastic or vinyl furniture D

Do not dry clothes on radiators and remove infrequently worn clothing from the bedroom D

Recommendations on the use of pollen avoidance measures

Nasal Filters (see: www.nasalairguard.co.uk), [47] B

Minimizing early morning activity when the greatest pollen is emitted - after the dew dries after sunrise to late morning D

Avoiding going out after thunderstorms or on windy days when dust and pollen are blown about. D

Wearing wraparound sun glasses. D

Not mowing the grass, and staying inside when it is being mown. If mowing is unavoidable, wear a mask. D

Planning holidays to avoid the pollen season. D

Keeping windows closed both at home and particularly when in the car. In particular keeping windows closed at night to prevent pollens or moulds from drifting into the home. Instead, if needed, use air conditioning, which cleans, cools and dries the air.

D

If the patient is sensitised to a particular plant or tree – consider removal. D

Shower and wash hair once home D

Bathing eyes and douche nose frequently D

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http://www.nasalairguard.co.uk/


Staying indoors when the pollen count or humidity is reported to be high D

Bringing in washing before pollen levels increase in the evening D

Recommendations on cat allergen avoidance measures

Remove cat, followed by thorough cleaning of house, steam cleaning walls, shampooing carpets D

Keeping cat out of bedroom and other commonly used rooms D

Washing cat weekly D

Removing carpets and replacing with hardwood floors and cleaning regularly D

Laminar airflow over bed at night B

Increase ventilation with fans, air-conditioning OR by opening windows D

* The grade of recommendation against use is A. This measure may be useful if used as part of a range of measures to reduce HDM exposure.

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Table 8 Effect of therapies on rhinitis symptoms (adapted from (Van Cauwenberge and others 2000))

SUGGEST HARSHA ADDS THE DATA ON INS?DECONGESTANT COMBOs TO THIS TABLE. GS

Sneezing Rhinorrhoea

Nasal obstruction Nasal itch Eye symptoms

H1-antihistamines Oral ++ ++ + +++ ++ Intranasal ++ ++ + ++ 0 Eye drops 0 0 0 0 +++Corticosteroids Intranasal +++ +++ +++ ++ ++Chromones Intranasal + + + + 0Eye drops 0 0 0 0 ++Decongestants Intranasal 0 0 ++++ 0 0 Oral 0 0 + 0 0Anticholinergics 0 ++ 0 0 0Antileukotrienes 0 + ++ 0 ++Intranasal steroids and Intranasal anti-histamine 1

+++ +++ ++ +++ +++

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Table 9: Oral antihistamines licensed in the UK according to age

AgeNon-sedating Antihistamine Sedating Antihistamine

> 6 months Alimemazine (Trimeprazine)

> 1 year Desloratadine Hydroxyzine hydrochlorideClemastineChlorphenamine

> 2 years Cetirizine hydrochloride (SAR only)Rupatadine

Cyproheptadine hydrochloride

Loratadine Promethazine hydrochlorideKetotifen

> 6 years Fexofenadine hydrochloride (SAR only)Cetirizine hydrochlorideLevocetirizine hydrochloride

> 12 years AcrivastineMizolastineFexofenadine hydrochlorideBilastine

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Table 10 Summary of Subcutaneous and Sublingual Immunotherapy

SCIT SLIT

Clinical Effectiveness Effective at lowering symptoms, medication use and quality of life in a Cochrane review (ref 5)

Efficacy demonstrated up to 3 years post discontinuation (ref 20)

Effective at lowering symptoms, medication use and quality of life in a Cochrane review (ref 10)

Efficacy demonstrated up to 2 years post discontinuation (ref 21,22)

Major Contra-indications Asthma: BTS/SIGN step 2 or above

Beta-blockers

Not to be initiated in pregnancy

Asthma: BTS/SIGN step 2 or above

Beta-blockers

Not to be initiated in pregnancy

Convenience Typically 4-7 pre-seasonal injections for each of 3 years for allergoid.

For continuous SCIT approximately 25 injections in first year, 12 maintenance injections per year thereafter

Received in specialist clinic with resuscitation facilities

Grazax® is commenced 4 months before the pollen season, then taken daily for 3 years.

Some SLIT vaccines taken for only approx. 5 months per year (e.g. Oralair®)

Taken in the home setting, with first dose in specialist clinic with resuscitation facilities

SafetyLocal reactions Pruritus and swelling at injection site Oropharyngeal pruritus and swelling

Systemic reactions Small risk of anaphylaxis, 0 fatalities (Cochrane)*

Minimal risk of anaphylaxis, 0 fatalities (Cochrane)*

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Milder reactions may include: nausea, abdominal pain, rhinitis, conjunctivitis, headache, cough

* No fatalities reported in UK since CSM review 1986, since the exclusion of severe/uncontrolled asthmatics and SCIT administration in specialist clinics

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Appendix A1: Levels of evidence (British Thoracic Society 2003)

Level of evidence Definition

1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias

1+ Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias1- Meta-analyses, systematic reviews, or RCTs with a high risk of bias2++ High quality systematic reviews of case control or cohort or studies

High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal

2+ Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal

2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal

3 Non-analytic studies, e.g. case reports, case series4 Expert opinion

Table A2: Grades of recommendations (British Thoracic Society 2003; Shekelle and others 1999)

Grade of recommendation

Type of Evidence

A At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population;orA body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results

B A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results;orExtrapolated evidence from studies rated as 1++ or 1+

C A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results;orExtrapolated evidence from studies rated as 2++

D Evidence level 3 or 4;orExtrapolated evidence from studies rated as 2+

E Recommended best practice based on the clinical experience of the guideline development group

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Appendix Evidence table – Recent combination therapy for rhinitis

Bibliogra-phic citation

Study type

Evidence level

No. patients

Patient characteristics

Interven-tion

Compa-rison

Length of follow-up

Outcome measures

Effect size

Source of funding

Has the study provided answers to the original question?

Weakness / limitations

Cited Y/N

Carr W 2012 JACI (Carr and others 2012b)

Meta-Analysis

1+(Grade A) 3398

12 or above. Mod-Sev SAR Dymista

Az/FP/Pl 14 days

Primary rTNSS change Time to response

minus 5.7 mean r TNSS MEDA

Yes-combination Az/FP better than individual drugs alone None Y

Carr W 2012 Allergy Asthma Proc (Carr and others 2012c)

Doub- blind placebo-control

2+(Grade C) 610

12 or above. Mod-Sev SAR Az vs FP vs Pl 14 days

primary rTNSS change. Secondary r T O S S

Az as good as FP overall in treating nose and eye. FP better for rhinorroea. At 14 days more volunteers eyes improved in Az group than FP

post-hoc analysis from previous study on Dymista vs AZ/FP/PL Y

Meltzer EO 2012 Allergy Asthma Proc (Carr and others 2012c)

Doub- blind placebo-control

2+(Grade C) 779

12 or above. Mod-Sev SAR Dymista

Az/FP/Pl 14 days

primary rTNSS change. Secondary r T O S S Time to onset of action and 12 hour r individual nasal symptom scores Eye QOL MEDA

Yes Time to onset action 30 minutes vs placebo. Dymista particulary decreaed nasal congestion compared to FP and Az used alone. Dymista overall better at treating eyes than FP alone and possibly just better than Az alone. None Y

Baroody F Am J Rhinol Allergy(Baroody and others

Doub- blind placebo-control 4 way X-over

2-(Grade C) 21

18-50 yrs NAC out of season in SAR

FF+OP vs FF/PL vs PL/OP vs PL/PL

4 way x over

Pre-Rx groups 1 week and then NACX2

Symptoms nose and eye and nasal histamine and tryptase GSK

FF/OL no better than FF/PL. Suggests treating the nose with an INS is best for treating the nasal

Small numbers NAC out of season is artificial Y

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2013)

ocular reflex. BUT if done in SAR will OL drops in eye act on effects of pollen in the conjunctiva

Bernstein D Ann Allergy Asthma Immunol 2012 (Bernstein and others 2012)

Pooled data from 4 DBPC studies

2+(Grade C) 962

12 or above. Mod-Sev SAR subgroup

MF-only looked at. Placebo 15 days

Ear and palate itch MSD

Yes. Decreases itch mouth and ears

post-hoc analy from previous studies. Confined only to MF Y

Baroody F JACI 2011 (Baroody and others 2011a)

Doub- blind placebo-control 4 group parallel

2+(Grade C) 60 PAR

Oxy vs Oxy/FF vs FF vs Pl

Parallel 4 groups

Rx 4 weeks + 2 weeks FU

TNSS and Acoustic Rhinometry GSK

FF/Oxy better than Oxy or FF alone or placebo in decreasing TNSS including congestion score.. AR shows FF/oxy better than oxy alone. Oxy adds to FF effects on nose.

Small numbers Y

Meltzer EO 2013 Am J Rhinol (Meltzer and others 2013)

Unblinded, single dummy for MF, placebo control for MF NOT Oxy

2-(Grade C) 705 SAR

MF + OXY different doses vs MF vs Oxy vs Placebo

vs baseline TNSS TNSS MSD

MF/OXY (both doses) same efficacy and better than Oxy or placebo alone. Faster onset of action than just MF alone (MF still as good fro relieving TNSS to same level as MF/OXY combinations

Blinding/Placebo/single dummy Y

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Intermittentsymptoms

< 4 days per weekor < 4 weeks at a time

Persistentsymptoms

> 4 days per weekand > 4 weeks at a time

Mild

Normal sleepNormal daily activities

Normal work and schoolNo troublesome symptoms

Moderate-severeOne or more items

Abnormal sleepImpairment of daily activities,

sport, leisureProblems caused at school or

workTroublesome symptoms


Figure 1 Classification of allergic rhinitis. Each box may be further subclassified into seasonal or perennial.

Se

105

Allergen

Mast cell

B cell

T cell(mast cell) Eosinophil

IL-4

IL-3, -5

GM-CSF

VCAM-1

IgE

IMMEDIATE RHINITISSYMPTOMS Itch, sneezing Watery discharge Nasal congestion

CHRONIC RHINITIS SYMPTOMS Nasal blockage Nasal hyper-reactivity

HistamineTryptaseLeukotrienesProstaglandinsBradykininPAF


Figure 2 Mechanism of allergic rhinitis

106


Figure 3 Treatment of allergic rhinitis (Rhinitis guideline 1st Edition)

107

Check use, compliance, dose +/or OC

Rx failure

Key:IN=intranasalOC= oral corticosteroidsα-H1= antihistamineLTRA= leukotriene

receptor antagonist

*Spray or drops

Diagnosis by history ± SPT/Serum specific IgEAllergen / irritant avoidance ± douching

Oral/topical Non-sedatingα-H1

Topical nasal corticosteroid

* Rx failure

Rx failure

moderate/severe

Rx failure

Blockage

mild

?infection/structural problem

Surgicalreferral

CatarrhAdd LTRA if asthmatic

or IN azelastine

Itch/sneezeAdd

IN azelastine or non sedating oral anti-H1

Watery rhinorrhoeaAdd ipratropium or

IN azelastine

Add (briefly)-decongestant-or OC-or longer term:INS+ IN azelastine

Consider immunotherapyif Sx predominantly due to one allergen

Symptoms

Rx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failure

Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure

Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure Rx failure

Rx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failureRx failure


Figure 4 Intranasal steroids bioavailability (proposed by Harsha Kariyawasam – to be decided)

108

• Nasonex Summary of Product Characteristics. 2011 • Rhinocort: Summary of Product Characteristics. 2011 • Beconase Summary of Product Characteristic 2011• Daley-Yates P et al Br J Clin PharmPharmacol 2001

• Kariyawasam H and Scadding GK Journal of Asthma and Allergy 2011• Scadding GK Paediatric Drugs 2008• Homer JJ, Gazis TJ. BMJ 1999

(BetamethasoneNose Drops)


Figure 5 Treatment of NAR ….

109

Anti-inflammatory:INS, IN antiH1,

both together

Eosinophilic

a) Ipratropium for rhinorrhoea

b) Capsaicin

No inflammation


Figure 6 Correct procedure for the application of nasal sprays (Rhinitis guideline 1st Edition)

1. Shake bottle well

2. Look down

3. Using RIGHT hand for LEFT nostril put

nozzle just inside nose aiming towards

outside wall

4. Squirt once or twice (2 different

directions )

5. Change hands and repeat for other side

6. DO NOT SNIFF HARD

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111

Figure 7 Classification of rhinitis causation in children - BSACI Rhinitis Guideline (subject to permission Roberts 2013)

Allergic rhinitis

Infectious rhinitis

Non-allergic, non-infectious rhinitis

Pre-school School Adolescent

Rhinitis symptoms that are associated with exposures to an allergen to which

the patient is sensitised.

Secondary to infection

Irritant exposure (e.g. exhaled tobacco smoke), gastroesophageal reflux and in older children, hormonal (hypothyroidism, pregnancy), drug-induced (e.g. beta-blockers, contraceptives, NSAID), neurogenic or vasomotor, idiopathic.


112

Different pathophysiologies may co-exist, particularly allergic rhinitis and infectious rhinitis.

Figure 8 BSACI Rhinitis Guideline

Classic Symptoms and signs of

rhinitis

Potential atypical presentations

Rhinorrhea – clear or discoloured discharge, sniffingPruritus – nose rubbing, the allergic salute, allergic crease, sneeze, may be associated with complaints of an itchy mouth or throat in older childrenCongestion – mouth breathing, snoring, sleep apnoea, allergic shiners

Pre-school School Adolescent

Eustachian tube dysfunction – ear pain on pressure changes (e.g. flying), reduced hearing, chronic otitis media with effusion

Cough – often mislabelled as asthmaPoorly controlled asthma – may co-exist with asthmaSleep problems – tired, poor school performance, irritabilityProlonged and frequent respiratory tract infections

Rhinosinusitis – catarrh, headache, facial pain, halitosis, cough, hyposmiaPollen-food syndrome, particularly with pollen driven allergic rhinitis

social history · web viewassociation of skin test reactivity, specific ige, total ige, and...

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