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 CXR sensitivity is only 50%, classically shows \200\230ring shadows \200\231 and \200\230 tramlines \200\231 \200\224indicating thickened airways, and the \200\230gloved \201 nge r \200\231 appearance. consolidation around thickened and dilated airways HRCT chest is 97% sensitive in detecting disease. Expiratory scans may be useful to demonstrate post-obstruc tive air trapping, indicative of small airways disease. Typically shows airway dilatation t o the lung periphery, bronchial wall thickening, and the airway appearing larger than its a ccompanying vessel (signet ring sign). If the bronchiectasis is localized to a single lobe, CT is useful to determine whether a central obstructing lesion is present. Contiguous 3-mm slices are needed to exclude a central airway lesion if there is associated haemoptysis. S ymptoms correlate with wall thickening and mucous plugging on CT scan. Traction bronchiecta sis seen in UIP is airway dilatation secondary to airway distortion, seen with chronic seve re interstitial \201 brosis Sputum microbiology Standard M, C & S (including for atypical organisms), acid-fast bacilli, and Aspergillus Pulmonary function tests with reversibility testing Immunoglobulins A, M, E, G (including IgG subclasses, if total IgG is low) Aspergi llus precipitins See p 467. \200 \200 CLINICAL FEATURES AND DIAGNOSIS 153 Second-line investigations \200 CF genotyping (see p 206) \200 Autoantibodies (ANA, RhF , dsDNA) if associated arthritis/connective tissue disease Vaccination response to tetanus, Haemophilus in \202 uenzae, and pneu- mococcal antibodies, if underlying immunosuppressio n suspected Skin tests/RAST to identify speci \201 c sensitizers (usually Aspergillus) Det ailed immunological investigation (including neutrophil and lymphocyte function studies) Br onchoscopy to exclude a foreign body if suggested by CT; obtain microbiological samples if unusual clinical presentation, or failure to respond to standard antibiotics Nasal brushing s/biopsy (in tertiary center) to assess ciliary beat frequency with video microscopy Saccha rin test The time for saccharin to be tasted in the mouth after deposition of a 0.5-mm part icle on the inferior turbinate of the nose. Normal is less than 30 min. A poor man \200\231 s cilial function test A1-antitrypsin levels if de \201 ciency is suspected Barium swallow /oesophageal imaging if recurrent aspiration suspected. \200 \200 CHAPTER 19 Bronchiectasis 154 General management The main aims of management are: \200 \200 Treatment of any underlying medical condition Prevention of exacerbations and progression o f underlying disease by physiotherapy. The options for airway clearance include: \200 \200 Postural or autogenic drainage Active cycle of breathing technique \200\224this involves br eathing control with forced expiration (huf \201 ng) using variable thoracic expansion Cou gh augmentation \200\224using \202 utter valves/cough insuf \202 ator/ high-frequency os cillation Exercise regimes \200\224important to prevent general deconditioning The physioth erapist is also vital during admission for exacerbations to help clear tenacious sputum Neb ulized hypertonic saline may improve airway clearance, although there is no RCT data to sup port its use \200 Reduction of bacterial load and prevention of secondary airway in \202 ammation and damage , with antimicrobial chemotherapy Supportive treatment \200\224treatment of associated air \202 ow obstruction Optimize nutrition Refer for surgery if necessary \200\224localized re section of affected area Refer for transplantation if indicated. \200 \200 \200 Antimicrobial chemotherapy \200 This may be intermittent for exacerbations only (for mild disease) or long term for more se vere disease. Antibiotics may be oral, nebulized, or intravenous Regular sputum surveillanc e will ensure the likely colonizing organism is known In vivo sensitivity may be different to in vitro sensitivity Patients need a higher antibiotic dose and for a longer time period (usually 2 weeks minimum) than people without bronchiectasis Antibiotic treatment choice d epends on the severity of the underlying disease Treatment response is usually assessed by a fall in sputum volume, and change to mucoid from purulent or mucopurulent sputum, with an improvement in systemic symptoms, spirometry, and CRP Pseudomonas-colonized patients have more frequent exacerbations, worse CT scan appearances, and a faster decline in lung functi on. \200 Progressive bacterial colonization Different bacteria colonize the airways at different sta ges of the disease, and their attempted eradica- tion and suppression is vital to the treat ment of bronchiectasis. The usual order of colonization is: \200 Staphylococcus aureus \200 Haemophilus in \202 uenzae \200 Moraxella catarrhalis \200 Pseudomonas species. GENERAL MANAGEMENT 155 Exacerbation treatment An exacerbation is usually a clinical diag- nosis, with an increase in sputum volume and tenacity, with discoloration. It may be associated with chest pain, ha emoptysis and wheeze, and sys- temic upset \200\224fevers, lethargy, and anorexia. The CRP may be elevated. Treatment depends on the potential pathogens and resident \202 ora. Nebu lized bronchodilators and regular physiotherapy (as an in- or out- patient) may also be nee ded. Exacerbation of mild bronchiectasis \200 \200 Antibiotics for exacerbations only (tailored to the colonizing organism) 2-week course of o ral cipro \202 oxacin at 750 mg bd if Pseudomonas aeru- ginosa colonized If early relapse, with a return to purulent sputum within 6 \200\2238 weeks, consider long-term oral antibio tics, e.g. amoxicillin 500 mg bd or doxycycline 100 mg od. If treatment failure, change to appropriate intravenous anti biotics, until clinical improvement. Exacerbation of more severe bronchiectasis Chronic suppressive antibiotics aim to prevent p rogression of disease, by reducing bacterial load and preventing ongoing in \202 ammation, thereby reducing morbidity and improving quality of life. \200 Antibiotics are usually given for at least 2 days after the sputum has cleared \200\224ofte n for 2 weeks If oral antibiotics fail, intravenous treatment is required. This may mean in -patient admission, or could involve long-line insertion, patient educa- tion in self-admin istration of intravenous antibiotics, and involvement of a home care team. First isolate of Pseudomonas aeruginosa (see also p 211) \200 Initial treatment is often aggressive with a 4 \200\2236 week course of oral cipro \202 ox acin 500 \200\223750 mg bd, and concurrent nebulized aminoglycoside, such as colistin 1 \200\2232 mega units bd If this fails and the patient still has Pseudomonas on sputum cultu re, intravenous antibiotics, usually an aminoglycoside and anti-pseudomonal penicillin (min imum 2 weeks), is required Consider long-term therapy with regular nebulized aminoglycoside to reduce levels of Pseudomonas and reduce subsequent exacerbations and airway in \202 am mation. Macrolide antibiotics have both anti-bacterial and immunomodulatory properties and have gre ater immunosuppressive effects than cortico- steroids. They decrease mucous production, alt er in \202 ammatory mediator release, and inhibit Pseudomonas virulence factors and bio \201 lm formation. Five small trials have reported bene \201 cial effects of macrolides in bron- chiectasis, with reduced sputum volume, improved lung function, and symptoms. The dr ugs are well tolerated, though concerns have been raised about non-tuberculous mycobacteria l resistance with long-term use. Azithromycin 250 mg on alternate days or 3 times weekly, o r 500 mg twice weekly (with LFT monitoring) are possible regimes. Risk of hearing loss. See p 162 (bronchiolitis). CHAPTER 19 Bronchiectasis 156 Further management \200 Self-management plan \200\224patients need an individual plan for exacerbations, which usua lly involves having a supply of home antibiotics Treatment of associated air \202 ow obstr uction/wheeze with inhaled steroids and/or bronchodilators There is no speci \201 c treatm ent for abnormalities of mucociliary function, although B2 agonists may enhance airway clea rance Nebulized DNase (Dornase alpha) \200\224no evidence for the use of this in non-CF bro nchiectasis, but it may be useful in severe exacerbations if the sputum is very tenacious a nd expectoration is dif \201 cult Nebulized hypertonic saline (7%) may aid sputum clearanc e N-acetylcysteine Annual in \202 uenza and pneumococcal vaccinations Osteoporosis prophyl axis (if on long-term steroids) Re \202 ux treatment if aspiration Immunoglobulin replacem ent therapy Patients found to have immunoglobulin de \201 ciency should be referred to an immunologist for further assessment. Intravenous immunoglobulin replacement therapy is usua lly given once or twice monthly, as a day case Surgery This is the only potential curative treatment, with resection of a single chronically infected lobe occasionally being of bene \201 t. It is less commonly needed now, as the incidence of single-lobe disease related to previous severe childhood pneumonia is falling. Surgery may be indicated for life-threaten ing haemoptysis Transplant is most commonly performed for CF bronchiectasis, but referral m ay be warranted for severe non-CF-related disease. \200 \200 \200 \200 \200 Complications of bronchiectasis \200 \200 Infective exacerbation Haemoptysis \200\224small volume haemoptysis (increasing during exac erba- tions) is common Massive haemoptysis (usually from tortuous bronchial arteries around damaged lung, e.g. bulla) is a life-threatening emergency (see p 40) Pneumothorax Respirat ory failure Brain abscess (now very rare) Amyloidosis. \200 \200 \200 FURTHER MANAGEMENT 157 Bronchiectasis and Aspergillus \200 Allergic bronchopulmonary aspergillosis (ABPA) \200\224excessive immune response to environ mental fungus Aspergillus (most commonly Fumigatus species); may be the cause of bronchiect asis (suspect particularly if upper lobe disease), as mucus plugs become impacted in distal airways, causing airway damage and subsequent dilatation. See p 468 Aspergilloma \200\224A spergillus may colonize damaged airways with formation of a fungus ball (mycetoma) within a previously formed cavity. This is extremely dif \201 cult to treat. Most commonly it caus es systemic upset and haemoptysis. See p 474. Further information Prolonged antibiotics for purulent bronchiectasis in children and adult s. Cochrane Database Syst Rev 2007/; 2: CD001392 This page intentionally left blank 159 Chapter 20 Bronchiolitis Pathophysiology and causes 160 Management 162 CHAPTER 20 Bronchiolitis 160 Pathophysiology and causes De \201 nition and epidemiology Bronchioles are small airways o f diameter <2 mm, lined by bronchial epithelium and with no cartilage in their walls. Termi nal bronchioles lead to alveoli. Many bronchioles need to be affected by disease before a p atient becomes symptomatic, when there will be increased airway resistance unresponsive to B2 stimulants. Bronchiolitis is poorly understood and is a mixture of conditions. Disease seems to affect bronchioles in two main ways: Affecting the bronchioles in isolatio n, with non-speci \201 c injury causing subsequent epithelial damage and in \202 ammation , e.g. viral bronchiolitis As a bronchiolitis associated with other airway disease, where t he bronchiolitis may be more of an incidental \201 nding along with other pathologies, e. g. COP, hypersensitivity pneumonitis, RB-ILD, Langerhans cell histiocytosis Pathophysiology is unclear. There is probably an initial injury to the epithelium of the br onchioles with subsequent in \202 ammation. Adjacent alveoli are often also involved. Ther e are two main pathological patterns of bronchiolitis. Both can exist in the same patient. \200 Proliferative bronchiolitis More common of the two patterns. Non-speci \201 c reaction to bronchiolar injury, with organizing exudate within the bronchiolar lumen. Proliferation of intraluminal \201 brotic buds, called Masson bodies, seen in bronchioles, alveoli, and al veolar ducts. Associated alveolar wall in \202 ammation and foamy macrophages in alveolar spaces. May completely or partially resolve. Tends to be more responsive to steroids. The p athology merges with that of COP (see p 270) Constrictive bronchiolitis Less common. Concen tric narrowing of the bronchiolar wall due to cellular in \201 ltrates 9 smooth muscle hyp erplasia, which may cause extrinsic compression, obliteration, distortion, mucus collection , peribronchiolar \201 brosis, and scarring. Patchy in distribution. Typically progressiv e and unresponsive to steroid therapy. Usually leads to respiratory failure and death. In practice, these are the commonest situations in which a diagnosis of bronchiolitis is us eful: \200 \200 \200 \200 \200 \200 Viral bronchiolitis (RSV) Post-lung transplant (obliterative bronchiolitis) Post-bone marro w transplant Connective tissue disease (usually rheumatoid arthritis) In association with i nterstitial lung disease and airways disease Diffuse panbronchiolitis (including Japanese p anbronchiolitis). PATHOPHYSIOLOGY AND CAUSES 161 Causes of bronchiolitis Proliferative bronchiolitis (associated with organizing pneumonia) Commoner causes \200 \200 \200 \200 COP (see p 270) Hypersensitivity pneumonitis (see p 249) Chronic eosinophilic pneumonia (se e p 232) Connective tissue disease \200\224rheumatoid arthritis, polymyositis, dermatomyosi tis (see p 185) Post bone marrow, heart, and lung transplant Organizing acute infection \200\224mycoplasma, Legionella, in \202 uenza, CMV, HIV, PCP. \200 Rarer causes \200 \200 \200 \200 \200 \200 \200 \200 ARDS (see p 101) Vasculitides, including Wegener \200\231s granulomatosis (see p 649) Drug- induced reactions, such as L-tryptophan, busulfan, cocaine Chronic thyroiditis Ulcerative c olitis Radiation or aspiration pneumonitis Distal to bronchial obstruction Common variable immunode \201 ciency syndrome. Constrictive bronchiolitis Commoner causes \200 Connective tissue disease, particularly rheumatoid arthritis, especially women in their 50s and 60s, with longstanding rheumatoid arthritis May be related to penicillamine therapy In fection \200\224viral (adenovirus, RSV, in \202 uenza, para-in \202 uenza), mycoplasma. Rarer causes \200 \200\230Chronic rejection phenomenon \200\231 in heart, lung, bone marrow transplants \200 \224affects up to 65% of lung transplant patients after 5 years post-transplant and is the primary cause of late death, bronchiolitis obliterans syndrome (see p 328). Patients taking statins post- transplant have a lower incidence of this; reasons unclear Diffuse panbronch iolitis (including Japanese panbronchiolitis). Following inhalation injury: mineral dusts, such as asbestos, silica, iron oxide, aluminum oxide, talc, mica, coal, sulfur dioxide, nit rogen oxide, ammonia, chlorine, phosgene \200\224may develop cough days to weeks after expo sure Drug reaction Hypersensitivity reactions Ulcerative colitis Cryptogenic. Rare, mostly women >40. Cough and dyspnoea. PFT: progressive air \202 ow obstruction and air trapping. KCO decreased, no bronchodilator response. \200 \200 \200 \200 CHAPTER 20 Bronchiolitis 162 Management Clinical features Insidious onset of cough and dyspnoea over weeks to months. Th ere may be an associated medical history, such as a transplant, connective tissue disease, or vasculitis, or a history of mineral dust or drug exposure. Possible history of recent vi ral illness. Investigations \200 PFTs Obstructive defect may be found, with no bronchodilator reversibility, particularly in constrictive bronchiolitis. Proliferative bronchiolitis can cause a restrictive or mixed d efect CXR can be normal or may show hyperin \202 ation, especially with con- strictive bro nchiolitis, diffuse in \201 ltrates with proliferative bronchiolitis, which may be migrato ry HRCT is helpful and may be performed prone in full expiration. (Prone CT is used to mini mize any gravity-dependent changes.) Normal bronchioles are too small to be seen; indirect signs of disease may be hyperin \202 ation, air trapping, causing a mosaic pattern and sub segmental atelectasis. Bronchioles with thickened walls due to in \202 ammation and dilata tion may be seen. CT is also useful to assess for signs of associated interstitial lung dis ease Open or thoracoscopic lung biopsy may be required to make the diagnosis, as transbronc hial biopsies are usually inadequate. The small airways need particularly carefully examina tion. Management \200 \200 \200 Treat any underlying disorder Cough suppressants Long-term macrolide antibiotics, such as e rythromycin 200 \200\223600 mg/day may improve symptoms, lung function, and mortality, espe cially in those with diffuse panbronchiolitis and cryptogenic bronchiolitis. Erythromycin l owers the neutrophil count by an unknown mechanism and reduces the number of lymphocytes St eroids are effective in cases of proliferative bronchiolitis and can treat the associated o rganizing pneumonia. They may also be bene \201 cial in bronchiolitis due to inhalation in jury, both in early and later stages. Relapses of the bronchiolitis may occur on stopping t he steroids. Bronchiolitis: speci \201 c conditions Diffuse panbronchiolitis/Japanese panbronchiolitis This is a distinct condi- tion and used to be thought of as rare outside Japan. Described 3 0 years ago in Japan, it is recognized there as a condition involving both the upper and lo wer respiratory tracts, with bronchiolar in \202 ammation and chronic sinusitis. An infect ious etiology was postulated as the cause of this disease, but no particular organism has b een consistently found. It can be familial and is associated with HLA-B54 (speci \201 c to East Asians) and A11. More prevalent in men, mean age at presentation 45, occurs particula rly in non- smokers, and chronic sinusitis can precede the chest symptoms often by years. M ore recently, a very similar clinical condition has been increasingly described outside Jap an and where sinusitis is less commonly found. This diffuse version is also an idiopathic i n \202 ammatory and suppurative disorder MANAGEMENT 163 of the respiratory bronchioles causing progressive and severe airways obstruction. It is pr esumably very similar to the Japanese variety and prob- ably under-recognized. Most of thes e patients have a productive cough with purulent sputum, exertional dyspnoea, wheeze, and w eight loss. There may be signs of progressive respiratory failure and cor pulmonale with cr ackles and wheezes on auscultation. \200 PFTs are obstructive, although may show a mixed pattern, with minimal airway hyperresponsiv eness. kCO is reduced CXR and CT may show diffuse ill-de \201 ned nodules (sometimes \200 \230tree- in-bud \200\231), bronchiectasis, and air trapping Sputum cultures may repeatedly show growths of Haemophilus in \202 uenzae, Pseudomonas aeruginosa, and less commonly Str eptococcus pneumoniae, Klebsiella pneumoniae, or Staphylococcus aureus. These should be tre ated, but can be hard to eradicate Cold agglutinins may be positive, mycoplasma tests are n egative BAL shows marked neutrophilia Open or thoracoscopic lung biopsy, although this may not be consid- ered necessary in areas where panbronchiolitis is prevalent. Bronchiolar his tology is characteristic, although not pathognomonic, with transmural in \201 ltrate of ly mphocytes, plasma cells, and foamy macrophages. The intraluminal exudates may be organized to form a polypoid plug. \200 \200 Treatment with low-dose erythromycin 400 \200\223600 mg/day for 2 \200\2236 months, and in some Japanese studies over 2 years, confers a signi \201 cant survival bene \201 t, most likely related to its anti-in \202 ammatory and immunomodula- tory effects (inhibits many cytokines), as well as reducing mucin secretion, rather than through its antibacterial effe cts. Untreated, 50% 5-year mor- tality. Azithromycin 250 mg three times a week may be a sui table alterna- tive. Relapses occur, but usually respond to macrolides again. Acute bronchiolitis This is a seasonal epidemic infective illness, common in infants <1 yea r, who present with coryza, low grade fever, cough, wheezing, tachypnoea, respiratory distr ess, hyperin \202 ation, and tachycardia. It is most commonly caused by respiratory syncyt ial virus (RSV), but also adenovirus, in \202 uenza, para-in \202 uenza, rhinovirus, huma n metapneumo virus, mycoplasma, and Chlamydia. In adults, acute bronchiolitis is caused by the same organisms, but is less severe. \200 CXR may be normal or show hyperin \202 ation, occasionally with patchy opacities, consolid ation, and collapse Histologically there is acute and chronic in \202 ammation of bronchio les, with necrosis, sloughing, oedema, and in \202 ammatory exudates in the bronchiolar lu men. Treatment is supportive, with oxygen, \202 uids. Steroids and bronchodilators may be give n if severe, but systematic reviews in children show no signi \201 - cant outcome bene \201 t. Further information Ryu JH et al. Bronchiolar disorders. Am J Respir Crit Care Med 2003; 16 8: 1277 \200\22392 Smyth RL, Openshaw PJ. Bronchiolitis. Lancet 2006; 368: 312 \200\22322 Poletti V et al. Diffuse panbronchiolitis. Eur Respir J 2006; 28: 862 \200\22371 This page intentionally left blank 165 Chapter 21 Chronic obstructive pulmonary disease (COPD) De \201 nition, etiology, pathology, clinical features 166 Investigations 168 Non-pharmaco logical management of stable COPD 170 Pharmacological management of stable COPD 172 COPD ex acerbations 176 Management of exacerbations 178 Surgical treatment 180 1-antitrypsin ( 1 -AT) de \201 ciency 182 166 CHAPTER 21 Chronic obstructive pulmonary disease De \201 nition, etiology, pathology, and clinical features COPD is common and is mostly du e to smoking. Patients with COPD represent a large proportion of in-patient (approximately 12% of all general medical admissions) and out-patient work for the chest physician. De \201 nition \200 \200 \200 \200 Fixed air \202 ow obstruction Minimal or no reversibility with bronchodilators Minimal var iability in day-to-day symptoms Slowly progressive and irreversible deterioration in lung f unction, leading to progressively worsening symptoms. Etiology 95% of cases are smoking-related, typically >20 pack years. COPD occurs in 10 \200 \22320% of smokers, indicating that there is probable genetic susceptibility. COPD is incre asing in frequency worldwide, particu- larly in some developing countries, due to high leve ls of smoking. It can also be caused by environmental and occupational factors such as dust s, chemicals, and air pollution. Pathology \200 Mucous gland hyperplasia particularly in the large airways, with mucous hypersecretion and therefore a chronic productive cough. Other mucosal damage from smoke: \200 Squamous metaplasia Replacement of the normal ciliated columnar epithelium by a squamous ep ithelium Loss of cilial function This leads to impairment of the normal func- tioning of th e mucociliary escalator, another reason for the chronic productive cough Chronic in \202 ammation and \201 brosis of small airways, characterized by CD8 lymphocy te, macrophage, and neutrophil in \201 ltration, with release of pro-in \202 ammatory cyt okines. Recurrent infections may perpetuate airway in \202 ammation Emphysema due to alveo lar wall destruction causing irreversible enlargement of air spaces distal to the terminal bronchiole (the acinus), with subsequent loss of elastic recoil and hyperin \202 ated lung s \200 Panacinar emphysema can occur with dilated air spaces evenly distributed across acinii Cent riacinar or proximal emphysema can occur with dilated air spaces found in association with the respiratory bronchioles Periacinar or paraseptal emphysema can occur with dilated air s paces at the edge of the acinar unit and abutting a \201 xed structure, such as the pleur a or a vessel Thickened pulmonary arteriolar wall and remodeling occur with hypoxia. Leads to increased p ulmonary vascular resistance, pulmonary hypertension, and impaired gas exchange. The cause of the increase in airways resistance and hence expiratory \202 ow limitation i s multifactorial. Small airway in \202 ammation reduces the airway lumen. Emphysema destro ys the radial attachments to the small airways, which normally hold them open and resist dy namic compression. DEFINITION, etiology, PATHOLOGY, AND CLINICAL FEATURES 167 COPD is increasingly being recognized as having features not only of pulmonary, but also sy stemic in \202 ammation and this may be the cause of the comorbidities found in patients w ith COPD. Daily activities are often modi \201 ed to avoid dyspnoea, which can lead to dec onditioning, muscle weakness, and wasting, meaning standing and walking become even harder. This leads to a vicious cycle of inactivity. Clinical features \200 \200 \200 \200 Dyspnoea Productive cough Decreased exercise tolerance Wheeze. Signi \201 cant air \202 ow obstruction may be present before the patient is aware of it. Signs depend on the severity of the underlying disease. \200 \200 \200 \200 \200 \200 \200 \200 Raised respiratory rate Hyperexpanded/barrel chest Prolonged expiratory time >5 s, with pur sed lip breathing Use of accessory muscles of respiration Quiet breath sounds (especially i n the lung apices) 9 wheeze Quiet heart sounds (due to overlying hyperin \202 ated lung) P ossible basal crepitations Signs of cor pulmonale and CO2 retention (ankle oedema, raised J VP, warm peripheries, plethoric conjunctivae, bounding pulse, polycythaemia. Flapping tremo r if CO2 acutely raised). Further information NICE guidelines for COPD. February 2004. www.nice.org.uk ERS Consensus Statement \200\224optimal assessment and management of COPD. ERJ 1995; 8: 139 8 \200\223420 MacNee W, Calverley PMA. Management of COPD. Thorax 2003; 58: 261 \200\2235 www.copd-international.com, www.lunguk.org/copd. Patient information websites 168 CHAPTER 21 Chronic obstructive pulmonary disease Investigations Pulmonary function tests \200 \200 Obstructive spirometry and \202 ow-volume loops Reduced FEV1 to <80% predicted (FEV1 is t he measurement of choice to assess progression of COPD, but it correlates weakly with the d egree of dyspnoea. Changes in FEV1 do not re \202 ect the decline in a patient \200\231s h ealth) FEV1/FVC <0.7 Minimal bronchodilator reversibility (<15%, usually <10%) and minimal steroid reversibility (how to perform these, see p 175). It is not neces- sary to test thes e in most patients, but is useful if there is diagnostic uncertainty or if the patient is t hought to have both COPD and asthma Raised total lung volume, FRC, and residual volume beca use of emphy- sema, air trapping, and loss of elastic recoil Decreased TLCO and kCO because presence of emphysema decreases surface area available for gas diffusion. \200 CXR is not required for diagnosis and repeated CXR is unnecessary unless other diagnoses ar e being considered (most importantly lung cancer or bronchiectasis). \200 Hyperin \202 ated lung \201 elds with attenuation of peripheral vasculature \200\224 \200\230black lung sign \200\231. More than 7 posterior ribs seen Flattened diaphragms (bes t CXR correlate of post-mortem degree of emphysema) More horizontal ribs May see bullae, es pecially in the lung apices, which if large can be mis- taken for a pneumothorax due to the loss of lung markings (CT can differentiate). \200 Consider checking 1-antitrypsin levels (see p 182), FBC to ensure not anemic, TFT if undu ly breathless. CRP is slightly increased in COPD, but decreases after steroid treatment. It may be related to the presence of comorbidities and may aid the assessment of the systemic effects of COPD, particularly in the research setting. Diagnosis is based on the history o f smoking and progressive dyspnoea, with evidence of irreversible air \202 ow obstruction on spirometry. Asthma is the most important differential diagnosis. Asthma is steroid and b ron- chodilator responsive. Nearly all patients with COPD will have a smoking history; this is not universal in asthma. Symptoms are common under the age of 35 in asthma; rare in COP D. Chronic productive cough is common is COPD and uncommon in asthma. Breathlessness is pro gressive and persistent in COPD, but variable in asthma. In asthma there is signi \201 can t diurnal or day-to-day variability of symptoms, and night-time waking with SOB or wheeze a re common; these symptoms are uncommon in COPD. Some patients have both. INVESTIGATIONS 169 COPD severity according to NICE guidelines 2004 (which differ slightly from the GOLD guidelines) Mild FEV1 50 \200\22380% predicted. May or may not be symptomatic with cough or sputum Moderate FEV1 30 \200\22349% predicted. Increased FRC, reduced TLCO Likely to be symptomatic (cough, sputum, dyspnoea), often managed by patient \200\231s GP Severe FEV1 <30% predicted. Marked hyperin \202 ation, TLCO usually low. Usually hypoxic, with si gns of cor pulmonale. Symptomatic, often needing hospital admissions MRC dyspnoea scale 1 Not troubled by breathlessness except on strenuous exercise 2 Short of breath when hurryi ng or walking up a slight hill 3 Walks slower than contemporaries on level ground because o f breathlessness or has to stop for breath when walking at own pace 4 Stops for breath afte r walking about 100 m or after a few minutes on level ground 5 Too breathless to leave the house, or breathless when dressing or undressing. BODE Index Variable Points on BODE index 0 1 2 3 FEV1, (% predicted) Distance walked in 6 min (m) \211 65 50 \200\22364 36 \200\22349 \211 35 \211 350 250 \200\223349 150 \200\223249 \211 149 MRC dyspnoea scale 0 \200\2231 2 3 4 Body mass index \211 21 \211 21 This is a simple multidimensional grading system for COPD, using BMI, air \202 ow Obstruct ion, Dyspnoea and Exercise capacity as its scoring variables. It has been shown to be bette r than FEV1 at predicting risk of hospitalization and death in patients with COPD. Patients are scored as having a BODE index of between 0 and 10, with higher scores indicating a hig her risk of death. It is being widely used, particularly in research studies (Celli BR et a l. NEJM 2004; 350: 1005 \200\22312). 170 CHAPTER 21 Chronic obstructive pulmonary disease Non-pharmacological management of stable COPD Aims of COPD management should include: \200 \200 \200 \200 Ensuring the diagnosis is correct Stopping smoking Optimizing treatment by minimizing sympt oms where possible Helping the patient maintain their quality of life. Management should be delivered by a multi-disciplinary team. No treatment has yet been show n to modify disease progression in the long term, except for stopping smoking. Smoking cess ation is the only intervention that is proven to decrease the smoking-related decline in lu ng function. All patients with COPD who smoke should be encouraged to stop at every opportu nity. Figure 21.1 shows the accelerated decline in FEV1 in susceptible smokers and the dela y in this acceleration from stopping smoking; susceptible smokers, however, never regain th e original curve. Nicotine replacement therapy should be used to aid smoking cessation (see p 730). Never smoked or not susceptible to smoke 100 ) 5 2 75 e g a t a Smoked regularly and susceptible to its effects e u l a v Stopped at 45 50 f o % ( Disability 25 1 V E F Stopped at 65 Death 0 25 50 75 Age (years) Fig. 21.1. Modi \201 cation of the Fletcher \200\223Peto diagram of FEV1 decline in suscep tible smokers Education can improve ability to manage illness and stop smoking. Pulmonary rehabilitation is a multidisciplinary program, with RCT evidence that it improves exercise tolerance, qual ity of life, and reduces hospital admissions. Muscle mass, particularly in the lower limbs, is reduced in people with COPD compared with age-matched healthy controls. This is an inde pendent predictor of mortality and disability, independent of the severity of the underlyin g lung disease and may re \202 ect the systemic nature of COPD. The mainstay of rehabilita tion is graded exercise to improve muscle function, but also includes breathing techniques and education. NON-PHARMACOLOGICAL MANAGEMENT OF STABLE COPD 171