Antibiotics \200\224only if infective element to the exacerbation. Most exacer- bations are due to viruses, especially the common cold. C. pneumoniae and M. pneumoniae are also impli cated. IV \202 uids \200\224patients are often dehydrated. Hypokalaemia (due to B2 ago- n ists) must be corrected. IM adrenaline \200\224may be useful if near arrest, whilst waiting for ITU support. ITU referral Liaise with ITU early! Better to discuss early a patient who does not subsequently need ITU input, than to \201 nd you and your patient in dif- \201 culty, with no ITU bed. There is no evidence to support the use of NIV in the management of asthma. Hypercapnic respirat ory failure in acute severe asthma is an urgent indication for endotracheal intubation. HOSPITAL TREATMENT OF ACUTE ASTHMA 131 When to discuss with ITU \200 \200 \200 \200 \200 \200 \200 Worsening PEF despite treatment Worsening hypoxia Hypercapnia Falling pH Exhaustion/poor re spiratory effort Drowsiness/confusion Respiratory arrest. Discharge Consider discharge when: \200 Reduced B2 agonist dose \200 Off nebulized drug s and on inhalers \211 24 h \200 PEF \211 75% predicted or best \200 Minimal PEF diur nal variation \200 Appropriate education has been given. Prior to discharge consider \200 \200 \200 \200 \200 Reason for the exacerbation. Could it have been avoided? Check patient \200\231s self-manag ement plan/asthma action plan Check inhaler technique (p 686) Book an appointment with GP o r practice nurse for within 24 h Book chest clinic appointment. CHAPTER 18 Asthma 132 Chronic asthma: management Aim to minimize symptoms and prevent exacerbations, prevent the poten- tial consequences of longstanding airway in \202 ammation leading to airway remodel ing and chronic unresponsive airway obstruction, and improve quality of life. The emphasis should be on education, self-management, and personal asthma action plans. Aim for: \200 \200 \200 Minimal day and night symptoms No exacerbations Normal lung function and prevention of lung function decline with the development of \201 xed air \202 ow obstruction No limit to p hysical activity Minimum steroid dose. \200 Treatment is based on disease severity using a step up/step down approach, starting treatme nt at the level appropriate to disease severity, based on the history, spirometry, and medi cation usage. The main aims during out-patient review are: \200 Ensure the diagnosis is correct and that symptoms are due to asthma and not coexistent/alte rnative pathology (e.g. re \202 ux, hyperventilation syndrome, etc.) Aim for no symptoms/n ormal lung function on minimal treatment Ensure an action plan is in place for exacerbation s Identify patients at risk of an adverse outcome. \200 \200 Pharmacological management British Thoracic Society Guidelines for the Management of Asthma Step 1 \200\224mild intermittent asthma \200 \200 Short-acting B2 agonist Check compliance, inhaler technique (including Volumatic or other s pacer), and eliminate potential triggers 10 puffs per day (2 or more canisters/month) is a marker of poorly controlled disease. Step 2 \200\224regular preventer therapy \200 \200 \200 Start at 400 g/day beclomethasone (BDP) in a twice daily dose Titrate steroid dose to sym ptoms, aiming for lowest effective dose Local steroid side-effects only (oral candida, dysp honia) from BDP \211 800 g per day Possible dose-related bone density effects at this d ose or above Fluticasone (Flixotide ) provides equal clinical activity to budesonide (e.g. Polemicist ) at half dosage. Mometasone (Asmanex ) is a new inhaled steroid; the current limited evidence suggests it is equivalent to twice the dose of BDP. Ciclesonide (Alvesco ) is another new inhaled steroid. It is a pro-drug, and the available evidence suggests it may have fewer local oropharyngeal side effects and less systemic activity than convention al inhaled steroids. The clinical bene \201 t and ef \201 cacy to safety ratio data have not been fully established. \200 CHRONIC ASTHMA: MANAGEMENT 133 Qvar (beclomethaosne diproprionate) has a smaller particle size and may be of bene \201 t in some, 400 g bd is as effective as \202 uticasone 500 g bd Step 3 \200\224add on therapy \200 If taking 200 \200\223800 g/day inhaled steroid, consider long-acting B2 agonist. A combi nation preparation may be appropriate If there is no response to a LABA, stop it and increa se the inhaled steroid The combination of an inhaled corticosteroid and LABA is now license d as maintenance and reliever therapy, if a rapid onset LABA, e.g. formoterol (Oxis ) is u sed, in the context of a personal asthma action plan. It is not clear if this is superior t o more conventional doses of inhaled steroid and LABA. Step 4 \200\224Poor control on moderate dose inhaled steroid and add on therapy: addition o f fourth drug \200 Ensure de \201 nite bene \201 t is obtained from any of these subsequent drugs before con tinuing Leukotriene receptor antagonist \200\224about a third of patients respond. May be u seful if atopic or for exercise-induced asthma. Trial for 1 month and stop if there is no r esponse. Also indicated in allergic rhinitis \200\224so consider if this is present as well Theophylline (has side-effects, e.g. nausea, and needs therapeutic drug monitoring) Slow-r elease oral B2 agonist. Step 5 \200\224Continuous or frequent use of oral steroids \200 NB Risk of side-effects if on oral steroids for >3 months or 3 \200\2234 courses per year W arn patient of potential side-effects (hypertension, diabetes, cataracts, gastric erosions) and ask GP to monitor. Start osteoporosis prophylaxis with calcium and vitamin D, or a bis phosphonate. Document baseline bone densitometry in those receiving prednisolone for more t han 3 months (see p 678). See www.rcplondon.ac.uk Aim for the lowest possible dose steroid. CHAPTER 18 Asthma 134 Chronic asthma: additional treatment options Steroid-sparing drugs, e.g. methotrexate, oral gold, and ciclosporin \200\224may be useful if other treatments are unsuccessful. They may reduce long-term steroid requirements, but a ll have side-effects and need hematological surveillance. There are very few data to suppor t their use, and signi \201 cant variability in response. Guidelines suggest a 3-month tri al, once other drugs have proven unsuccessful, with treatment in a center with experience o f their use. Continuous subcutaneous terbutaline infusion via a portable syringe driver may be useful. Standard dose is 5 mg over 24 h, but up to 15 mg/24 h may be given. Use terbuta line nebulizer solution (2.5 mg/mL) e.g. for 10 mg/24 h, use 4 ml of nebulizer solution, wi th 6 ml of saline, infuse the 10 ml over 24 h. Bene \201 cial effects have been reported i n severe asthma, but safety and ef \201 cacy have not been assessed in RCTs. Best responde rs may be those with marked PEFR variability ( \200\230type 1 brittle asthmatics \200\231) to allow steroid reduction. Omalizumub Recombinant humanized monoclonal antibody against IgE has been shown to reduce e arly and late asthmatic responses after allergen challenge, and is now licensed for atopic individuals with dif \201 cult to control disease, in combination with other standard trea tments. The drug removes circulating and tissue IgE by promoting loss of high af \201 nity IgE receptors on mast cells, basophils, and dendritic cells, leading to reduced airway in \202 ammation. Compared with placebo, it has been shown to reduce exacerbation rates, with improvement in asthma symptoms and quality of life scores, but with no overall change in l ung function. Meta- analyzes suggest a reduction of around 100 g of inhaled corticosteroi d is achieved per day compared with placebo. Omalizumub is given as a subcutaneous injection every 2 \200\2234 weeks. The dose depends o n the patient \200\231s weight and serum IgE concentration; the peak response is at 12 \200 \22316 weeks and two-thirds of patients respond. The serum IgE should be 30 \200\223700 IU (there is a high risk of anaphylaxis at higher IgE levels). There is some debate as to whether the high cost of the drug can be justi \201 ed. The 200 7 NICE guidelines suggest its use for severe persistent allergic asthma, which is unstable despite optimized standard therapy, and should be used for a trial period of a maximum of 1 6 weeks, ceasing if there is no clinical response. Additional points \200 Regular review \200\224to ensure patients are on appropriate treatment for their disease se verity, and are maintained on the lowest possible inhaled steroid dose. Step down treatment if patient stable for 3 months or more. Step down inhaled steroid by reducing dose by 25% at 3-monthly intervals. CHRONIC ASTHMA: ADDITIONAL TREATMENT OPTIONS 135 Asthma action plan \200\224all patients with severe asthma should have an agreed written as thma action plan (self-management plan), their own peak \202 ow meter, and regular checks on compliance and inhaler technique. A self-management plan should include speci \201 c a dvice about recognizing loss of asthma control and action to take if asthma deteriorates. P atients on low dose inhaled steroids (200 g) should have their dose increased \201 ve-f old at the start of an exacerbation. This should not be extrapolated to higher inhaled ster oid doses. The previous recommendation of doubling the dose of inhaled steroid at the start of an exacerbation is unproven. Monitoring morbidity \200\224the 3 RCP questions In the last week or month: \200 Have you had dif \201 culty sleeping because of your asthma symptoms (including cough)? Ha ve you had your usual asthma symptoms during the day (cough, wheeze, chest tightness, or br eathlessness)? Has your asthma interfered with your usual activities (e.g. work, housework) ? Further information Walker S. Anti-IgE for chronic asthma. Cochrane Database Syst Review 20 03; 3: CD003559. Holgate ST. Ef \201 cacy and safety of anti-immunoglobulin-E antibody (omalizumab) in seve re allergic asthma. Clin Exp Allergy 2004; 34: 632. CHAPTER 18 Asthma 136 Non-pharmacological management Allergen avoidance may reduce severity of disease in sensiti zed indi- viduals. House dust mite control measures need to be comprehensive \200\224 there is no current evidence to support it, although trials are ongoing. Pet removal may be usef ul, if the history is suggestive, and sensitivity has been demonstrated by skin prick testi ng or raised speci \201 c IgE levels. Smoking cessation may reduce asthma severity. Curren t and previous smoking reduces the effect of inhaled steroid; these individuals may need hi gher steroid doses. Complementary therapies No current evidence exists. Dietary manipulatio n No consistent evidence and none supported by interventional trials. Low magnesium intake is associated with increased asthma prevalence. Fish oils may be bene \201 cial. Weight re duction in obese asthmatics leads to improved control. Immunotherapy Desensitization using allergen-speci \201 c immunotherapy may be bene \201 cial in a small subgroup of patients . Buteyko breathing technique is a series of breathing exercises that mimic yoga breathing techniques. One study showed a reduction in the use of inhaled bronchodilator and steroid u se in asthmatics carrying out these exercises, with no change in lung function or bronchial hyperrespon- siveness. Cochrane review of breathing exercises concluded that there was no evidence of improvement in lung function, but improved quality of life scores. NON-PHARMACOLOGICAL MANAGEMENT 137 Future developments New steroids Research for \200\230dissociated steroids \200\231 is ong oing. These are steroids in which the useful anti-in \202 ammatory effects (mediated by tr an- scription factor inhibition) are dissociated from the side-effects (mediated via glucoc orticoid DNA binding). Safer steroids, e.g. ciclesonide, a new once-a-day inhaled steroid, appear to have an improved side-effect pro \201 le. Ciclesonide is a pro-drug, activated b y airway esterases, with fewer side- effects due to high degrees of protein binding. Eosinophil inhibitors A variety of approaches to inhibit eosinophil recruit- ment are under investigation, including adhesion molecule inhibition and eosinophil chemotactic receptor inhibition. Phosphodiesterase-4 inhibitors New generation phosphodiesterase (PDE)- 4 inhibitors, e.g. r o \202 umilast, are being investigated in clinical trials. These drugs have a broad anti-i n \202 ammatory action, with neutrophil inhibitory effects. Early clinical trial data look s promising. Cytokine modulators Tumor necrosis factor (TNF) \200\223alpha plays an impor- tant role in the pathogenesis of asthma. Anti-TNF antibodies have been bene \201 cial in the treatment of in \202 ammatory bowel disease and rheumatoid arthritis. Anti-TNF may be useful in the treatment of severe asthma, as it may block other important leukotrienes, e.g. IL-13. Bronchial thermoplasty This is the application of controlled radio- frequency energy to the airway wall, using a specialized catheter at bron- choscopy. It heats the tissue to about 65 C, reducing muscle mass in the small and medium-sized airways, with several airways tre ated under direct vision at each session. Three separate sessions are required to treat all accessible airways. This has been assessed in a small non-randomized study and is well tol erated. Improved asthma quality of life scores, reduced airway hyperresponsiveness, and red uced oral steroid doses are reported, with no reduction in hospital admissions. The mechani sm of action is unlikely to be improved airway contractility alone, and neurohumoral effect s are postulated. A small placebo controlled trial in 32 patients has shown signi \201 can tly worse initial symptoms and side-effects, but a small longer-term improvement at 22 and 52 weeks. Further information British Guideline on the management of asthma. Thorax 2003; 58: S1, upd ated 2007 Pavord ID et al. Safety and ef \201 cacy of bronchial thermoplasty in symptomatic severe a sthma. AJRRCM 2007; 176(12): 1185 \200\22391 http://www.brit-thoracic.org.uk/iqs/sid.06309940811162053801561/asthma.html \200\224a good site from which to download copies of the asthma guidelines in various formats and to obta in training information www.occupationalasthma.com www.ginasthma.com CHAPTER 18 Asthma 138 Dif \201 cult/refractory asthma Patients with refractory asthma are a small subgroup of as thma patients (5 \200\22310%). They have dif \201 cult to treat disease, re \202 ected by high maintenance medication requirements, or persistent symptoms and air \202 ow obstruc - tion, with multiple exacerbations, despite high medication use. They have high numbers of admissions, and cause signi \201 cant anxiety to their families and medical staff. There is a wide range of disease severity, including those with highly labile disease and those w ith severe, more chronic air \202 ow obstruction. No consensus de \201 nition. The disease is usually \200\230de \201 ned \200\231 on the basis of: \200 Medication requirements (typically continuous or near continuous oral steroids) Asthma symp toms Frequency of exacerbations Severity of air \202 ow limitation \200 \200 Patients exhibit the features of asthma, and it is thought that the air \202 ow obstructio n, airway hyperresponsiveness, and PEF diurnal variability are more severe in refractory di sease, though the physiological reasons for this remain unclear. These patients typically fail to completely reverse their air \202 ow obstruc- tion follow ing a 2-week course of oral prednisolone and demonstrate a poor bronchodilator response to inhaled B2 agonists. The pathological mechanism is likely to be ongoing airway in \202 ammation, with increasin g airway \201 brosis, but this is not proven. Other possibilities include steroid resista nce (see opposite), B2 receptor down-regulation, or a different disease process altogether. Whether they represent a different asthma \200\230phenotype \200\231 is unclear. Diagnosis of refractory asthma \200 Con \201 rm the diagnosis is correct \200\224this will mean going back through the notes a nd retaking a thorough history Con \201 rm reversible air \202 ow limitation now or in th e past (as for non- refractory asthma; see p 126) Consider other diagnoses for cough, breat hlessness, and wheeze, and investigate for potential exacerbating diseases: \200 \200 \200 \200 \200 \200 COPD/smoking Bronchiectasis/cystic \201 brosis Sinus disease \200\224consider ENT review Churg \200\223Strauss syndrome/eosinophilic syndromes \200\224consider ANCA Systemic diseas e \200\224thyroid disease or vasculitis Allergic bronchopulmonary aspergillosis \200\224con sider Aspergillus precipitins/skin tests/IgE Vocal cord dysfunction \200\224consider laryng oscopy Hyperventilation syndrome Gastro-oesophageal re \202 ux \200\224consider OGD/24 h p H Upper airway obstruction \200\224consider CT or bronchoscopy Obstructive sleep apnoea \200\224consider sleep study Obesity Cardiac dysfunction \200\224consider echo and/or cardi ological opinion \200 \200 \200 \200 \200 \200 DIFFICULT/REFRACTORY ASTHMA 139 Psychiatric/emotional issues/depression/secondary gain \200\224consider psychiatry or psych ology review Functional wheeze by breathing near residual volume Refractory asthma Before labeling a patient as \200\230refractory \200\231, compliance mus t be con \201 rmed. This may be by checking drugstore prescription records, using inhaler devices monitoring medication usage, or by measurement of plasma pred- nisolone or early mo rning cortisol levels. Treatment is that of non-refractory asthma, with inhaled long-acting B2 agonists and high-dose inhaled corticosteroids (see pp 132 \200\223136). Ensure treatme nt trials are adequate and adhered to. \200 In patients unable to tolerate a prednisolone dose <20 mg per day, corticosteroid pharmacok inetic studies may be useful. However, <25% of patients with severe asthma show clinically signi \201 cantly increased prednisolone clearance (usually a speci \201 c reason can be identi \201 ed, such as concomitant use of enzyme inducing medication). IM steroid, e.g. t ri- amcinolone 120 mg, may be useful if compliance is a major problem. Nebulized budesonide (Respules , 1 \200\2232 mg bd) may be of bene \201 t. In \202 ammatory markers, e.g. sp utum or plasma eosinophil counts or exhaled nitric oxide levels, may be useful to assess me dication response, although no trials have demonstrated their use clinically in this group of patients. Anti-in \202 ammatory and immunomodulating drugs (specialized center only). I nclude methotrexate, cyclosporin, oral gold, and intravenous gammaglobulin. None of these h ave been studied in a randomized controlled trial in this group of patients and none have d emonstrated improvement in airway hyperresponsiveness. Macrolide antibiotics have anti-in \202 ammatory and immune modulatory effects, reducing airway reactivity, and eosinophilic i n \202 ammation, and have been shown to reduce oral steroid requirements. Persistence of a irway infection by C. pneumoniae and Mycoplasma is increasingly recognized as a contributor y factor in persistent air \202 ow obstruction, and recurrent exacerbations and macrolide antibiotics may act in this situation to clear persistent infection. Use, e.g. azithromycin , 250 mg, on alternate days, or 3 times a week, or 500 mg twice weekly. Six-weekly LFT moni toring is required. Risk of hearing loss. \200 \200\230Steroid-resistant \200\231 asthma This subgroup of patients represents a very smal l proportion of refractory asthma patients. Middle-aged obese women, often with other addit ional diagnoses, are overrepresented in this group. They require supportive treatment, with out high doses of glucocorticoids. Diagnoses other than asthma are likely and investigation should be directed towards these. Whether they represent a further \200\230asthma phe- no type \200\231 is not clear. Further information Robinson DS et al. Systematic assessment of dif \201 cult-to-treat ast hma. ERJ 2003; 22: 478 \200\22383 Thomas PS et al. Pseudo-steroid resistant asthma. Thorax 1999; 54: 352 \200\2236 CHAPTER 18 Asthma 140 Asthma in pregnancy \200 \200 \200 \200 \200 \200 Pregnancy can affect asthma Asthma can affect the outcome of pregnancy Prognosis \200\2241/ 3 worsen, 1/3 improve, 1/3 no change Asthma course is likely to be similar in successive pr egnancies Severe asthma is more likely to deteriorate than mild asthma Most exacerbations o ccur late, in the second and third trimester, and are due to viral infections and non-adher ence to inhaled corticosteroid Pre-pregnancy counseling \200 \200 \200 \200 Asthmatics must continue normal asthma medication Give smoking cessation advice Monitor the pregnant asthmatic closely Severe exacerbations in pregnancy are associated with low birth weight infants, an effect similar to maternal smoking in pregnancy Acute asthma in pregnancy \200 \200 Risk to fetus of uncontrolled asthma outweighs any small risk of drugs Asthma medications a re generally safe in pregnancy Steroids should be continued Drug therapy as for non-asthmatics, including inhaled and oral corticos- teroids Maintain o xygen saturation >95% Continuous fetal monitoring for acute severe asthma Liaise with obste trician if acute severe asthma \200 \200 Leukotriene receptor antagonists Limited safety data available for use in pregnancy and it is recommended not to start using whilst pregnant. Continue in women who have previously de monstrated signi \201 cant improvement in disease control prior to pregnancy. Management during labor \200 \200 Acute asthma is rare in labor (probably due to high sympathetic drive) Close liaison betwee n the respiratory and obstetric teams is para- mount, with close fetal monitoring Managemen t should be as for non-pregnant individuals, see pp 132 \200\223136), maintaining the oxyge n saturation >95%. There is no RCT data for magnesium sulfate, although it is used in eclam psia Regional anesthetic blockade is preferable to general anesthesia Prostaglandin E2 may be safely used for induction of labor Prostaglandin F2 alpha (for post-partum bleeding) may cause bronchospasm Give parenteral hydrocortisone 100 mg 6 \200\2238-hourly during labor i f on oral prednisolone at >7.5 mg daily for >2 weeks prior to delivery \200 \200 ASTHMA IN PREGNANCY 141 Breast-feeding \200 An asthmatic mother may reduce the chance of atopy in her child by breast-feeding; current opinion is divided Prednisolone is secreted in breast milk, but the infant is exposed to on ly tiny and clinically irrelevant doses. CHAPTER 18 Asthma 142 Occupational asthma \200 This is asthma due to speci \201 c workplace sensitizers and may account for 10% of adult onset asthma The diagnosis is often dif \201 cult to make Early diagnosis is important, as earlier removal from the workplace in affected individuals leads to a better outcome It is different to asthma exacerbated by irritants in the workplace, and can occur in individual s with or without prior asthma. \200 Agents induce asthma through immunological and non-immunological mechanisms. Immunological disease appears after a latency period of exposure; thus it is necessary for the worker to be sensitized to the casual agent (e.g. acid anhydride \200\224baker s asthma). Non-immunol ogical disease is characterized by the absence of a latent period and occurs after accident al exposure to high concentrations of a workplace irri- tant. This is irritant induced asth ma (previously named reactive airways dysfunction syndrome), usually caused by exposure to, e.g. smoke, vapors, or fumes, with a strong temporal relationship between irritant exposur e and the development of asthma type symptoms. The latency between \201 rst exposure and symptom onset can be long, and depends on the sensitizing agent \200\224an accurate history therefore includes current and past exposures Once sensitized, re-exposure to very low con centrations can provoke symptoms May be associated with rhinitis and urticaria Improves awa y from work, but can take several days to settle. \200 Risk factors \200 \200 \200 Atopy HLA type (e.g. HLA-DQB1*0503 associated with isocyanate allergy) Smoking (especially for high molecular weight agents). Diagnosis \200 \200 \200 There are two useful screening questions: \200 Is your ast hma worse when at work? \200 Does your asthma improve when away from work or on holiday? Con \201 rm the diagnosis of asthma Con \201 rm the relationship between asthma and work exposures Find the speci \201 c cause Document lung function deterioration in the workplace, usually by serial peak \202 ow recording at work, at home, and on holiday. Bronchial provocation/challenge testing using suspected agent \200\224only in specialized c enters, but dif \201 culties with testing and producing a valid test substance mean that a negative speci \201 c bronchial challenge in a worker with otherwise good evidence of occ upational asthma is not suf \201 cient to exclude the diagnosis. Skin prick testing/speci \201 c IgE for certain sensitizers (although a positive test only indicates sensitization which can occur with or without disease). OCCUPATIONAL ASTHMA 143 Document \200 \200 \200 The range of chemicals used Working practices Use of personal protective equipment. Serial PEF recording in occupational asthma \200 Record every 2 h from waking to sleep \200 For 4 weeks, whilst no changes to treatment \200 Document home/work periods and any holidays \200 Analysis is best made by experts, usually using a criterion-based analysis system, e.g. OASYS (a computer program that plots and interprets serial peak \202 ow rec ordings; see www.occupationalasthma.com) Patients may be sensitized to more than one agent and over 300 agents are identi \201 ed. See wwww.asmanet.com Table 18.1 Causes of occupational asthma Sensitizing agent Occupational exposure Low molecular weight agents (act as haptens) Isocyanates Paint spraying, adhesives, polyurethane foams Acid anhydrides Epoxy paint, varnish, resins, baking Metals Welding, plating, metal re \201 ning Glutaraldehyde and other disinfectants Health care workers Drugs Pharmaceutical industry High molecular weight agents Amine dyes Cosmetics, hair dyes, rubber workers Wood dusts, bark Textile workers, joiners, carpenters Animal-derived antigens Vets, laboratory workers (20% affected) Biological enzymes Detergent industry, pharmaceuticals Plant products Bakers, hairdressers Fluxes, colophony Solderers, electronics industry CHAPTER 18 Asthma 144 Management of occupational asthma \200 \200 \200 \200 Identify the cause Remove the worker from exposure Continue employment if at all possible E arly diagnosis and removal from exposure are important factors for a good outcome Improveme nt in FEV1 may be maintained for one year following last exposure, and for up to 2 years fo r non-speci \201 c responsiveness The decision to remove the patient from the workplace sh ould not be taken lightly, and should be made by a consultant with experience of occupation al lung disease. The employee may be eligible for Disablement Bene \201 t (no proof of neg ligence is required). Latex allergy is seen in up to 18% of health care workers, and is the leading cause of occu pational asthma in this group due to the widespread use of latex gloves. It is potentially serious, with avocado, bananas, kiwi, and chestnuts cross-reacting to give a similar clinic al picture. Treatment is absolute avoidance; those affected should wear a MedicAlert bracel et and always use non-latex gloves. This page intentionally left blank CHAPTER 18 Asthma 146 Vocal cord dysfunction A proportion of patients labeled as having severe asthma, will have symp- toms originating from the upper airway. This can be due to vocal cord dysfunction (VC D) and/or so-called \200\230upper airway hyperresponsiveness \200\231; these are different , but overlap. VCD is likely to arise from interrelation- ships between laryngeal hyperresp onsiveness and autonomic imbalance, with inputs from potential aetiological/aggravating fac tors, such as re \202 ux, psychological stress, hypocapnia (hyperventilation). Increased l aryngeal hyperresponsiveness can occur following respiratory tract infections and possibly asthma itself. Upper airway hyperresponsiveness may include more than just the larynx, but this is not clear. Patients will typically present with asthma symptoms, with associated triggers, e.g. odors, cold air. They typically have no reduction in peak \202 ow or response to asthma medicat ions (though this is possible). A careful history will reveal shortness of breath that is of short duration, worse on inspi ration, and extremely sudden in onset, with symptom-free periods. Pathogenesis \200 \200 \200 \200 \200 \200 Recent URTI, may take months to settle Post-nasal drip/chronic sinusitis Gastro-oesophageal re \202 ux disease with micro aspiration Chronic laryngitis Hyperventilation in associati on with anxiety/panic It is postulated that the origin of the vocal cord closure may stem f rom a re \202 ex airway protective mechanism. Diagnosis is based on excluding other causes of cough and breathless- ness. It may be sugge sted by hearing a more stridulous noise and lack of basal wheeze. The gold standard is visu alization of abnormal vocal cord movement at laryngoscopy, where there is excessive adducti on of the anterior two-thirds of cords with the creation of a posterior \200\230glottic ch ink \200\231; although this \201 nding may not always be present at the time of study. Th e \202 ow volume loop should show inspiratory \202 ow limitation, with \200\230stutter ing \200\231 of the \202 ow. Treatment (for which there are no randomized controlled tria ls) \200 \200 \200 \200 \200 \200 \200 Speech therapy Panting (autopeep) Coughing and cough suppression techniques Inspiratory res istance devices HELIOX/nebulized saline/lidocaine spray Sedatives Exercise. Further information Newman KB et al. Clinical features of vocal cord dysfunction. AJRCCM 19 95; 152: 1382 \200\2236 Stanton AE, Bucknall CE. Vocal cord dysfunction. A review. Breathe 2005; 2: 31 \200\2235 (h ttp://www.ersnet.org/ers/LR/browse/viewPDF.aspx?id_attach=10896) This page intentionally left blank CHAPTER 18 Asthma 148 Allergic rhinitis (hay fever) This is the syndrome of nasal discharge or blockage with nasa l and/or eye itching, and sneezing. It is often associated with post-nasal drip, cough, fat igue, and with signi \201 cant morbidity. Allergic rhinitis is de \201 ned as perennial i f the symptoms occur year round and seasonal if occurring at a particular time of year. The prevalence is increasing and affects up to 15% of the UK population. Up to 30% of patients with persistent allergic rhinitis have asthma. Etiology The lining of the nose is in conti nuum with the lower respira- tory tract, and in \202 ammation of the upper and lower airwa ys often co- exists. Common aeroallergens provoking seasonal allergic rhinitis are tree pol len in the spring, and grass pollen in the summer months. Perennial rhinitis usually re \202 ects allergy to indoor allergens, such as house dust mite (the provoking allergen is a digestive enzyme that is shed in the feces), cat salivary protein, cockroaches, or animal dander. Pathophysiology Symptoms occur following the inhalation of allergen to which the su bject is sensitized, and against which they have IgE anti- bodies. These antibodies bind to mast cell IgE receptors, with the release of mediators, including tryptase and histamine, causing symptoms immedi- ately after exposure. Diagnosis is usually made from the history, which should identify the triggers to the disease. The main differential diagnosis is with sinusitis due to bacterial infection and upper airway involvement due to vasculitis. Asthma is common in association with rhinitis and treatment of rhino- sinusitis in association wi th asthma leads to improved asthma control. Up to 50% of asthma patients will have allergic rhinitis. Treatment \200 Allergen avoidance This may be easier said than done. It can take up to 20 weeks to remove cat allergen from a house. Keeping car and house windows shut and wearing sunglasses may he lp avoid pollen. Pollen counts are highest in the afternoon and early evening Non-sedating antihistamines, improve sneezing and itching, but have no effect on nasal blockage Topical intranasal steroid, e.g. budesonide triamcinolone Topical anticholinergics, e.g. ipratropiu m, may be useful for rhinorrhea, if uncontrolled with topical nasal steroids Topical sodium cromoglycate may be bene \201 cial, particularly for allergic conjunctivitis Decongestant s, e.g. oxymetazoline, may help, but rebound nasal blockage and tachyphylaxis are a potenti al problem if used regularly. Leukotrene receptor antagonists (e.g. montelukast) may be ben e \201 cial. \200 149 Chapter 19 Bronchiectasis Epidemiology, pathophysiology, and causes 150 Clinical features and diagnosis 152 General m anagement 154 Further management 156 CHAPTER 19 Bronchiectasis 150 Epidemiology, pathophysiology, and causes De \201 nition Irreversible abnormal dilatation of one or more bronchi, with chronic airway in \202 ammation. Associated chronic sputum pr oduction, recurrent chest infections, and air \202 ow obstruction. Epidemiology The preval ence of bronchiectasis is unknown, but is probably falling due to vaccinations and the impr oved and earlier treat- ment of childhood infections. However, the advent of HRCT scanning may now lead to the diagnosis of more subtle (and possibly subclinical) disease. Pathophysi ology An initial (usually infectious) insult is needed to damage the airways. Disordered an atomy leads to secondary bacterial colonization, perpetuating in \202 ammatory change and damaging the muco- ciliary escalator. This prevents bacterial clearance and leads to furthe r airway damage. Major airways and bronchioles are involved, with mucosal oedema, in \202 ammation, and ulceration. Terminal bronchioles become obstructed with secretions, leading t o volume loss. A chronic host in \202 am- matory response ensues, with free-radical format ion and the production of neutrophil elastase, further contributing to the in \202 ammator y process. Bronchial neovascularization occurs with hypertrophy and tortuosity of the bronc hial arteries (which are at systemic pressure), which may lead to intermittent haemoptyses. Etiology The causes of bronchiectasis are many and varied (see Table 19.1). In general, th e etiology is either a one-off infectious insult, or an underlying immune de \201 ciency. Determining the etiology of the con- dition may lead to different management if, for exampl e, the underlying cause is found to be cystic \201 brosis or an immune de \201 ciency. T he cause is idiopathic in around 50% of cases and these are likely to be due to an (as yet unidenti \201 ed) impairment in host defense. The most important cause to exclude is cystic \201 brosis (see p 205). Even relatively mi ld bronchiectasis diagnosed in middle age can be due to CF. The diagnosis can alter managem ent, with: \200 \200 Involvement of the multidisciplinary CF team Attention to other potential problems, e.g. ga strointestinal disease, sinus disease, diabetes Inheritance (relevant to the rest of the fa mily) Fertility issues. \200 Consider genotyping for CF if: \200 \200 \200 \200 \200 Predominantly upper lobe disease Haemophilus in \202 uenzae or Pseudomonas aeruginosa colo nization Malnutrition malabsorption, diabetes Family history of cystic \201 brosis or bronchiectasis Associated subfertility or infertility. A normal chloride sweat test does not exclude CF, as some mutations are associated with nor mal sweat chloride levels. The test is also dif \201 cult and subject to a number of techn ical errors. Only 90% of CF sufferers have a recognizable gene defect (there are over 1000 CFTR mutations). EPIDEMIOLOGY, PATHOPHYSIOLOGY, AND CAUSES 151 Table 19.1 Causes of bronchiectasis Genetic Cystic \201 brosis Congenital Pulmonary sequestration Post-infective Tuberculosis Whooping cough (if infection in a localized area) Severe pneumonia Non-tuberculous mycobacteria (NTM) \200\224there is some debate as to whether the bronchiec tasis seen in association with NTM (classically in elderly females) is caused by or seconda rily infected by NTM Immune de \201 ciency Primary \200\224hypogammaglobulinaemia Secondary \200\224HIV, CLL, nephrotic syndrome (Excessive immune response \200\224ABPA) Mucociliary clearance abnormalities Primary ciliary dyskinesia (see p 628) Kartagener \200\231s syndrome Young \200\231s syndrome (bronchiectasis, sinusitis, and azoospermia \200\224i.e. clinical features identical to those of CF) Toxic insults Aspiration Inhalation (toxic gasses, chemicals) Mechanical insults Foreign body aspiration Extrinsic lymph node compression Intrinsic (intraluminal) obstructing tumor Associations Bronchiectasis is associated with a number of systemic diseases, so cough and sputum produc tion in these conditions should trigger referral to determine the cause: Rheumatoid arthritis (up to 35% of RA patients have bronchiectasis) Connective tissue diseases, e.g. Sj gren \200\231s syndrome, SLE Ulcerative colitis and Crohn \200\231s disease (see p 248) Chronic sinusitis Yellow nail syndrome Marfan \200\231s syndrome CHAPTER 19 Bronchiectasis 152 Clinical features and diagnosis Suspect bronchiectasis in a patient with recurrent episodes of \200\230bronchitis \200\231 over several years prior to presentation. The clinical picture is one of: \200 Symptoms \200 Cough \200 Chronic sputum production (typically tenacious, purulent, and daily) Intermittent haemoptyses Breathlessness Intermittent pleuritic pain (usually in asso ciation with infections) Lethargy/malaise. \200 \200 \200 Signs \200 \200 Coarse inspiratory and expiratory crackles on auscultation Air \202 ow obstruction with wh eeze. Diagnosis is usually made clinically, with high resolution CT chest for con \201 rmation. Investigations are aimed at: \200 \200 Con \201 rming the diagnosis Identifying a treatable underlying cause for the bronchiectas is (possible in about 40%) Optimizing management to prevent exacerbations and further lung damage Essential investigations \200 