Pain from malignant chest wall in \201 ltration is often \200\230boring \200\231 in chara cter, and may disturb sleep; it is frequently not related to respiration. Causes include pr imary lung cancer, secondary pleural malignancy, mesothe- lioma, and rib or sternal involve ment from malignancy (including myeloma and leukemia) Chronic thromboembolic disease tends to present with breathlessness; when chest pain occurs , it is usually episodic, rather than persistent - As with acute pleuritic pain, investigat ions are directed by initial clinical suspicion. Consider CT chest, bone scan, serum autoan tibodies, full blood count and \201 lm, serum electrophoresis. CXR may appear normal in m alignant chest wall disease. This page intentionally left blank 11 Chapter 3 Chronic cough and normal CXR Etiology and clinical assessment 12 Treatment 14 Causes of cough (with or without CXR abnor mality) 15 Causes of chronic cough: asthma, GORD 16 Causes of chronic cough: rhinitis, post -infectious, ACE inhibitors, idiopathic 18 CHAPTER 3 Chronic cough and normal CXR 12 Etiology and clinical assessment Cough is a frequent symptom of many respiratory diseases a nd is often associated with underlying lung pathology and an abnormal CXR. Cough can occur in otherwise healthy people and is often a self-limiting symptom. Persistent coughing can b e a socially disabling and distressing symptom, for which help is often sought. Cough synco pe is loss of consciousness following violent coughing, a Valsalva type maneuver, which imp airs venous return to the heart and provokes bradycardia and vasodilatation (similar to an ordinary faint). Important as car drivers must cease driving until liability to cough synco pe has ceased, con \201 rmed by medical opinion; commercial drivers must cease driving and have no cough syncope or pre- syncope for 5 years if they have a chronic respiratory condi tion, including smoking. If they have asystole due to cough, driving can be considered afte r pacemaker insertion. \200 Acute cough = cough lasting less than 3 weeks, usually due to viral upper respiratory tract infection. May linger for 3 \200\2238 weeks as a \200\230post-viral cough \200\231 Chroni c cough = cough lasting more than 8 weeks Patients with a normal CXR and persistent cough a re often grouped under the heading \200\230chronic cough \200\231 It can sometimes be dif \201 cult to determine the underlying cause Susceptible individuals have a heightened coug h re \202 ex Investigation is warranted, but successful response to therapeutic trials may aid determination of the underlying cause. Centers vary in their approach to this Speciali st cough clinics suggest they achieve diagnosis and effective treatment in over 80% of pati ents referred with chronic cough. \200 \200 \200 Etiology In practice, over 90% of cases of chronic cough with a normal CXR are caused by on e or more of: \200 \200 \200 Cough variant asthma or eosinophilic bronchitis Gastro-oesophageal re \202 ux disease Post -nasal drip, due to perennial or allergic rhinitis, vasomotor rhinitis, or chronic sinusiti s. In clinic: full history can be unhelpful. Although cough is most commonly due to asthma, re \202 ux, or post-nasal drip, there may be no speci \201 c symptoms to suggest these diag noses. \200 \200 Duration of cough When it tends to occur \200\224night or early morning, after exertion, on exposure to dust, pollen, or cold air (asthma), after meals or on sitting or bending over (GORD), nocturnal (post-nasal drip and asthma) Non-productive or productive and, if so, how much sputum and color. Signi \201 cant amounts of sputum usually indicate a primary lung pathology Haemoptysis Fever \200 etiology AND CLINICAL ASSESSMENT 13 Associated symptoms: \200 \200 \200 \200 \200 Previous respiratory disease, such as childhood asthma, eczema, or hay fever History of sinus disease or perennial rhinitis Hi story of previous severe respiratory infections, such as whooping cough, that may have caus ed bronchiectasis Known cardiac disease or valvular heart disease Drug history ?ACE inhibit or Occupation ?Workplace irritants Pets/birds Smoker Use of recreational drugs. Shortness of breath or wheeze Throat clearing or sensation of post-nasal drip Chest pain An kle swelling/orthopnoea/paroxysmal nocturnal dyspnoea Dyspepsia \200 \200 \200 \200 \200 \200 Examination can also be unhelpful, as it is usually normal. Look for signs of underlying lu ng disease or other medical conditions, such as heart failure, neurological disease (partic ularly bulbar involvement). Investigations Initially \200 \200 Ensure CXR is normal Spirometry may indicate restrictive or obstructive defect. Performance of spirometry may provoke cough and bronchospasm Methacholine provocation test (p 769) pro vides the best positive predictive value for cough due to asthma. A lack of response sugges ts cough variant asthma is extremely unlikely. PC20 is normal in eosinophilic bronchitis Se rial peak \202 ow recordings twice daily for 2 weeks. Greater than 20% diurnal variation suggests asthma. Can be normal in cough variant asthma Induced sputum examination, if avail able, for eosinophil count, to suggest either asthma or eosinophilic bronchitis. Usually a research tool. Later \200 Consider chest HRCT if any features suggestive of lung cancer or interstitial lung disease, as a small proportion may present with a normal CXR (central tumor) Consider ENT examinati on if predominantly upper respiratory tract disease, resistant to treatment. Consider sinus CT Consider bronchoscopy if foreign body possible, or history suggestive of malignancy, sm all carcinoid, endobronchial disease. Perform after CT to help guide bronchoscopist Conside r oesophageal pH monitoring. CHAPTER 3 Chronic cough and normal CXR 14 Treatment The initial treatment of patients with a chronic cough is determined by what the most likely underlying cause is, based on the history and investi- gations. The key is to g ive any drug treatment at a high enough dose, and for a long enough time (such as 3 months) , to be effective. Symptomatic treatment for cough Over the counter medicines may provide relief, although the re is little evidence of a speci \201 c pharmacological effect. Below is a list of possibl e treatments: \200 \200 Honey and lemon \200\224home remedies Dextromethorphan \200\224a non-sedating opiate. Compo nent of many over the counter cough remedies. Dose response, with maximum cough re \202 ex suppression at 60 mg. (Benylin preparations, Actifed preparations, Vicks Vaposyrup p reparations, Sudafed Linctus , Night Nurse ) Menthol \200\224short lived cough suppressan t (Benylin preparations, Vicks Vaposyrup preparations) Sedative antihistamines \200\224 suppress cough, but cause drowsiness. Good for nocturnal cough Codeine or pholcodine \200 \224opiate antitussives \200\224codeine requires prescription. No greater ef \201 cacy tha n dextromethorphan and greater side-effect pro \201 le Opiates \200\224prescription. Low d ose morphine sulfate 5 \200\22310 mg showed signi \201 cant improvement in patients with i ntractable cough in RCT (Morice AH et al Am J Crit Care Med 2007). Side-effect pro \201 le of opiates, so should be used with caution. CAUSES OF COUGH (WITH OR WITHOUT CXR ABNORMALITY) 15 Causes of cough (with or without CXR abnormality) Respiratory \200 Infection: viral upper and lower respiratory tract infection, bacterial pneumonia, TB, pert ussis Chronic bronchitis Obstructive airways disease: COPD, asthma Cough variant asthma Eos inophilic bronchitis Obstructive sleep apnoea (nocturnal only) Lung cancer Bronchiectasis, cystic \201 brosis Interstitial lung disease Airway irritants: smoking, dusts and fumes, acute smoke inhalation Airway foreign body. \200 \200 \200 \200 \200 \200 \200 \200 \200 Mediastinal \200 External compression of trachea by enlarged lymph nodes (e.g. lymphoma, TB) Mediastinal tum ors/cysts/masses. Cardiac \200 \200 Left ventricular failure Left atrial enlargement (e.g. severe mitral stenosis). ENT \200 \200 Acute or chronic sinusitis Post-nasal drip due to perennial, allergic, or vasomotor rhiniti s. GI \200 \200 GORD Oesophageal dysmotility, stricture, or pharyngeal pouch causing repeated aspiration Oe sophago-bronchial \201 stula. CNS Neurological disease affecting swallowing causing repeated aspiration, such as stroke, multiple sclerosis, motor neuron disease, or Parkinson \200\231s disease. Drugs \200 \200 ACE inhibitors Some inhaled preparations can cause cough \200\224particularly ipratropium. Other \200 \200 \200 Idiopathic Ear wax (vagal nerve stimulation) Psychogenic/habitual. CHAPTER 3 Chronic cough and normal CXR 16 Causes of chronic cough: asthma, GORD Asthma or \200\230cough variant asthma \200\231, \200\230cough predominant asthma \200\231. This represents one end of the asthma spectrum, with airway in \202 ammation, but may have minimal bronchoconstriction. There is not alway s a typical asthma history, but ask about wheeze, atopy, hay fever, or childhood asthma or eczema. Cough may be the only symptom. Cough is typically worse after exercise, in cold air , or in the mornings. \200 Spirometry may be normal, without evidence of air \202 ow obstruction. There may be typica l asthmatic diurnal peak \202 ow variability of >20%, or peak \202 ows may be stable. M ethacholine challenge should be positive. If negative, other causes of cough should be soug ht. Treatment should be for at least 2 months, with high-dose inhaled steroids. Response ma y take days or weeks. Bronchodilators may make little difference. If inhaled steroid therap y has been tried unsuccessfully, ensure inhaler technique is optimal and a high dose has be en used. Alternatively prescribe a 2-week course of oral prednisolone 30mg/day and assess r esponse. If the cough improves, high-dose inhaled steroids should be continued and slowly r educed after about 2 months. Eosinophilic bronchitis Airway eosinophilia, rarely with perip heral blood eosinophilia, causing heightened cough re \202 ex, but no bronchial hyperrespo nsiveness/wheeze or peak \202 ow variation. Diagnosis based on negative asthma investigat ions and induced sputum eosinophilia. Improves with inhaled corticosteroids, usually after 2 \200\2233 weeks, or trial of oral prednisolone. Sputum eosinophil count also reduces with treatment. If there is no response, the cough is unlikely to be due to eosinophilic airway in \202 ammation. Gastro-oesophageal re \202 ux disease (GORD) Cough may be related to distal re \202 ux at the lower oesophageal sphincter (LOS) or due to micro-aspiration of acid into the trachea. There may be associated oesophageal dysmotility. LOS re \202 ux is often longstanding and is associated with a productive or non-productive daytime cough, and minimal nocturnal sym ptoms. It is worse after meals and when sitting down, due to increased intra-abdominal pres sure being transmitted to the LOS. Micro-aspiration is associated with more prominent sympt oms of re \202 ux or dyspepsia, although these are not always present. Patients may have a n intermittent hoarse voice, dysphonia, and sore throat. Cough may be the only symptom. Laryngoscopy may reveal posterior vocal cord in \202 ammation, but this is not a reliable sign. CAUSES OF CHRONIC COUGH 17 A trial of treatment for both is recommended. This is with a high-dose proton pump inhibito r for at least 2 months, although longer treatment may be required to control cough. H2 rec eptor blockers are also effec- tive and pro-kinetics like metoclopramide may help. Other re \202 ux avoid- ance measures should be carried out: avoiding caffeine, wearing loose \201 tting clothes, sleeping with an empty stomach (avoid eating <4 h before bed), sleeping propped up. Investigation, if required, due to either treatment failure or because of diag- nostic unce rtainty, is with 24 h ambulatory pH monitoring, which determines the presence of re \202 u x events. These may not necessarily be responsible for the cough, so it is not a very speci \201 c or sensitive test. Oesophageal man- ometry can be used to measure the LOS pressure and oesophageal contrac- tions after swallowing to determine the presence of oesophageal d ysmotility. CHAPTER 3 Chronic cough and normal CXR 18 Causes of chronic cough: rhinitis, post-infectious, ACE inhibitors, idiopathic Rhinitis and post-nasal drip Rhinitis is de \201 ned as sneezing, nasal discharge, or blockage for mor e than an hour on most days for either a limited part of the year (seasonal) or all year (p erennial). Rhinitis may be allergic (e.g. hay fever), non-allergic, or infective. The assoc iated nasal in \202 ammation may irritate cough receptors directly or produce a post-nasal drip. These secretions may pool at the back of the throat, requiring frequent throat clear ing, or drip directly into the trachea, initiating cough. A history of facial pain and puru lent nasal discharge suggests sinusitis, which can also predispose to post-nasal drip. Symp toms of cough can occur on lying, but can be constant, regardless of position. ENT examination may reveal swollen turbinates, nasal discharge, or nasal polyps. Treatment Nasal preparations should be taken by kneeling with the top of the head on the \202 oor ( \200\230Mecca \200\231 position) or lying supine with the head tipped over the e nd of the bed. \200 Non-allergic rhinitis Trials suggest the best results are with an initial 3 weeks of nasal decongestants with \201 rst-generation antihistamines (which have helpful anticholinergic properties) and pseudoephedrine. Alternatives are nasal ipratropium bromide or xylometazol ine. This is then followed by 3 months of high-dose nasal steroids, which are ineffective w hen used as \201 rst-line treatment. Second-generation antihistamines (i.e. non-sedating) are of no use in non-allergic rhinitis Allergic rhinitis Second-generation antihistamine a nd high-dose nasal steroids for 3 months at least Vasomotor rhinitis Nasal ipratropium brom ide for 3 months. Sinusitis is an infection of the paranasal sinuses, which may complicate an URTI and is fre quently caused by Haemophilus in \202 uenzae or Streptococcus pneumoniae. It causes fronta l headache and facial pain. Chronic sinusitis may require further investigation with CXR or CT, which shows mucosal thickening and air- \202 uid levels. Surgery may be indicated. \200 Chronic sinusitis Treat as for non-allergic rhinitis, but include 2 weeks of antibiotics ac tive against H. in \202 uenzae, such as doxycycline or co-amoxiclav. CAUSES OF CHRONIC COUGH 19 Post-infectious Respiratory tract infections, especially if viral in nature, can cause coug h. This may take weeks or months to resolve spontaneously, although most settle within 8 we eks. The cough is related to a height- ened cough re \202 ex. Associated laryngospasm can occur, which is a sudden hoarseness, with associated stridulous inspiratory efforts and a s ensation of being unable to breathe. Treatment with antitussives, such as codeine linctus, may ease the symp- toms. Inhaled ster oids have been tried, but there is no trial evidence that these work. ACE inhibitor cough o ccurs with any ACE inhibitor and is related to bradykinin not being broken down by angioten sin-converting enzyme, and accumulating in the lung. Occurs in 10% of people on ACE inhibit ors; more frequent in women. Can occur 3 \200\2236 months after starting the drug; the coug h may be initiated by a respiratory tract infection, but persists thereafter. Cough usually settles within a week of stopping the drug, but may take months. Avoid all ACE inhibitors thereafter and may need to change to an angiotensin receptor antagonist. Stop ACE inhibitor in any patient with a troublesome cough. Idiopathic cough accounts for 20% of referrals to a specialist cough clinic. It is diagnosed after a thorough assessment. Typically, there i s lym- phocytic airway in \202 ammation, but there may also be a history of re \202 ux co ugh. Further information BTS guidelines: Recommendations for the management of cough in adults. Thorax 2006; 61 (suppl 1) www.thoraxjnl.com Review Series on Cough. Morice A, Kastelik J. Thorax 2003; 58: 901 \200\2235; Fontana GA, P istolesi M, Thorax 2003; 58: 1092 \200\2235; Dicpinigaitis PV 2004; 59: 71 \200\2232; McGar vey LP 2004; 59: 342 \200\2236. Birring SS et al. Eosinophilic bronchitis: clinical features, management and pathogenesis. Am J Resp Med 2003; 2: 169 \200\22373. Irwin RS, Madison JM. The diagnosis and treatment of cough. NEJM 2000; 343: 1715 \200\22321 . This page intentionally left blank 21 Chapter 4 Critically ill patient with respiratory disease CHAPTER 4 Critically ill patient 22 Patients often present critically ill to the Emergency or the Acute Medical Department with respiratory disease. This may be due to a deterioration or exacerbation of an existing con dition, a \201 rst presentation of a previ- ously undiagnosed disease, or respiratory inv olvement of an acute sys- temic disease. As with any critically ill patient, standard manag ement is required initially to stabilize, with the focus moving to diagnosis and treat- men t. Often these need to take place in parallel. Depending on the pres- ence of any pre-exist ing respiratory disease and the nature and severity of this, it may be important to determi ne disease-speci \201 c treatment and/or treatment limitations, and senior physician input should be sought for this. 1. Initial assessment Airway \200\224is the patient maintaining their airway? Is there snor ing or gur- gling? Tilt head, lift chin, use suction if good views. Is an airway adjunct ne cessary? Consider inserting Guedel airway or nasopharyngeal airway if GCS reduced <8 (p 741 ). Consider calling ITU if intubation and ITU care likely to be necessary, or if the patien t is rapidly deteriorating/peri-arrest and full assessment has not yet been possible (p 689 ). Breathing \200\224cyanosis? What is the SaO2 and associated FiO2? \200 \200 \200 \200 Exclude tension pneumothorax clinically (p 382). What is the respiratory rate? Has a blood gas been taken and what does it show? (p 791) Oxygenation adequate? If not, likely to need increased FiO2 (p 704), or if this is already maximal, need ventilatory support \200\224inv olve ITU Is the CO2 low? If hyperventilation, already working hard breathing to maintain O2 at current level. May need to increase FiO2, or if already maximal, need ventilatory assis tance \200\224involve ITU Is the CO2 high (p 791)? Hypoventilating, tiring, or CO2 narcosis in COPD \200\224consider ventilatory support Request an urgent portable CXR. Circulation \200\224what is pulse rate, BP, rhythm on cardiac monitor/ECG? What is \202 u id balance status? Aim to optimize. Ensure IV access secured and blood tests sent. Look at BP, JVP, urine output, peripheral perfusion (capillary re \201 ll time). If they are hypot ensive, are they under \201 lled? Consider \202 uids (crystalloid). If they are euvolaem ic/over \201 lled but hypo- tensive with poor urine output, they may need inotropic suppo rt. Likely to need central venous access to enable CVP monitoring, and this will aid drug a dministration. Disability \200\224Conscious level: GCS or AVPU (alert, responsive to verbal commands, responsive to pain, unresponsive). Are they confused? Check blood glucose, tempe rature, pupils, signs of acute neurological disease \200\224 neck stiffness, plantar re \202 exes, tone. Examination \200\224temperature, sputum, asterixis, chest signs (pneumo- t horax, wheeze, silent chest, effusion, consolidation, pulmonary oedema), cardiac murmurs, p alpable abdominal organomegaly, skin/nail signs, rash Investigations \200\224immediate test s include FBC, clotting screen, CRP, U&E, blood cultures before antibiotics. CRITICALLY ILL PATIENT WITH RESPIRATORY DISEASE 23 2. Consider underlying cause If known respiratory disease, this will enable more targeted t herapy. Try and obtain recent hospital notes. Ask patient or their relatives about disease severity, current treatment, plans of clinicians for long-term care (immunosuppression, tra nsplant list, home NIV, advanced directive, lasting power of attorney, etc.). What is their usual current health status \200\224exercise tolerance, activities of daily living? What h as caused this deterioration \200\224a potentially reversible process (e.g. infection, drug s, pneumothorax, PE) or gradual progression of underlying disease? Review CXR and compare w ith old \201 lms if possible. \200 For more details regarding exacerbations of chronic lung diseases, see p 128 (asthma), p 71 4 (COPD), p 565 (CF), p 176 (bronchiectasis), p 216 (IPF), p 154 (lung cancer), p 264 (sick le cell). If no known respiratory disease, full history required to obtain diagnosis. The patient \200\231s cardiovascular status and illness severity will determine how brief/full this is. Ask about recent symptoms, travel, contact illness, risk factors for immunocompromise, usu al health status, drugs. For presentation-based differential diagnoses and initial investigation plans see p 3 (brea thlessness), p 8 (chest pain), p 40 (haemoptysis), p 67 and p 79 (immunocompromise), p 91 ( unexplained respiratory failure), p 29 (diffuse lung disease), p 25 (diffuse alveolar hemor rhage), p 45 (pleural effusion), p 61 (pregnancy), p 57 (post-operative), p 419 (pneumonia) , p 401 (pulmonary embolism), p 373 (pneumothorax), p 593 (toxic agents), p 639 and p 642 ( upper airway disease and anaphylaxis), and p 300 (SVCO). 3. Determine treatment aims In patients with known severe respiratory disease, with poor pr e- morbid state (e.g. very limited exercise tolerance, comorbidities, severe dementia), int ubation and invasive ventilation may not be appropriate. The patient may have their own vie ws on this or have made a living will/ advanced directive. Old notes should be reviewed if possible, and this decision should be discussed with their respiratory consultant or the co n- sultant on call. Non-invasive ventilation (p 693) may be appropriate. In patients with k nown respiratory disease, with an acute exacerbation (infective or non-infective), respirat ory and organ support may be indicated to enable them to survive this episode. This should be discussed with their respiratory consultant or the consultant on call and ITU. In patien ts with no known respiratory disease, respiratory and organ support may well be indicated t o enable them to survive this episode. This should be discussed with the consultant on call and ITU. If they have sig- ni \201 cant pre-existing comorbidity from a non-respiratory d isease (severe cardiac failure, severe dementia), the details of this should be ascertained and discussed with their usual consultant if possible. If there is any doubt about a patient \200\231s usual health status, or no previous history or notes available, or they are deteriorating before full assessment can be made, they sho uld be considered for full ventilatory and organ support. This page intentionally left blank 25 Chapter 5 Diffuse alveolar hemorrhage Diffuse alveolar hemorrhage 26 26 CHAPTER 5 Diffuse alveolar hemorrhage Diffuse alveolar hemorrhage A triad of: \200 \200 \200 Bleeding into the alveoli is o ften a feature of a small vessel vasculitis of the lungs. This blood tends to remain in the lungs and is not expectorated. Patients with diffuse alveolar hemorrhage may have a backgr ound history of vasculitis over the preceding weeks to months. They can present with slowly progressive dyspnoea with haemoptysis, or be acutely unwell with hypoxia. They may require ventilatory support. Presentation Abrupt onset haemoptysis is the most common symptom, alt hough this is not present in one-third of cases. Also cough, dyspnoea, low-grade fever, wei ght loss, arthralgia, myalgia. There may be a history of chronic sinusitis (Wegener \200 \231s). Examination May be non-speci \201 c, or may have signs of underlying vasculitis wi th skin rashes, nail fold infarcts, digital gangrene. Episcleritis, corneal ulceration, epi staxis, nasal crusting, or deafness may be present. Neurological signs including mononeurit is multiplex should raise the pos- sibility of vasculitis. Patients may be breathless. Haem aturia and proteinuria on urine dip. diffuse alveolar in \201 ltrates haemoptysis (although not always present) a fall in hemog lobin or haematocrit. Investigations \200 \200 \200 May be hypoxic \200\224check SaO2 ABG FBC \200\224?falling hemoglobin CXR showing bilate ral alveolar in \201 ltrates \200\224dif \201 cult to distinguish from pulmonary oedema o r infection Consider chest HRCT Raised kCO as increased intra-alveolar hemoglobin is availa ble to combine with carbon monoxide. Abnormal if raised by more than 30%. If breathless at rest, they will not be able to perform this test as it requires breath-holding of an air, c arbon monoxide, and helium mixture for 10 s. This test can be used to monitor disease progr ess BAL shows bloodstained lavage, which becomes sequentially more so with each washing. Cy tology shows haemosiderin-laden macrophages Renal involvement: blood and/or protein in the urine, red cell casts, raised urea and creatinine Send blood for urgent ANA, ANCA (PR3 and MPO), anti-GBM, dsDNA, and rheumatoid factor Consider biopsy of lung, kidney (if acute glom erulonephritis present), or other affected site if well enough to make a tissue diagnosis. Transbronchial biopsy specimens are usually insuf \201 cient to make a diagnosis of vascul itis and a surgical lung biopsy is required. Capillaritis (a neutrophilic vasculitis of cap illaries and venules), hemorrhage, or diffuse alveolar damage with hemorrhage seen on lung biopsy. \200 DIFFUSE ALVEOLAR hemorrhage 27 3 Management of alveolar hemorrhage \200 \200 Admit to hospital Supportive treatment, with intravenous \202 uids, blood transfusion, an d oxygen if necessary Monitor, paying particular attention to oxygen saturations and keepin g them above 92% with oxygen therapy. May need respiratory support with intubation and vent ilation or CPAP. Monitor hemoglobin and transfuse if necessary. Monitor urine output and re nal function Aim to establish the underlying diagnosis, usually with tissue biopsy Treatmen t with plasma exchange, high dose steroids and cyclophos- phamide, and dialysis if required . \200 Key questions \200 \200 \200 Is this isolated lung disease? Is there accompanying renal disease? Are there other feature s of an underlying disease? \200\224ENT, joints, etc. Causes of alveolar hemorrhage First three are most common Goodpasture \200\231s disease* We gener \200\231s granulomatosis* SLE* Rheumatoid arthritis Microscopic polyangiitis* Progres sive systemic sclerosis Mixed connective tissue disease Polyarteritis nodosa Beh et \200 \231s disease Essential mixed cryglobulinaemia Vasculitis: endocarditis- or tumor-related I diopathic rapidly progressive glomerulonephritis Idiopathic pulmonary haemosiderosis Drugs: D-penicillamine, cocaine Chemicals: trimellitic anhydride, lymphangiography Leptospirosis Isolated pauci-immune pulmonary capillaritis Coagulopathy, such as disseminated intravascul ar coagulation p 658 p 652 p 190 p 188 p 656 p 194 p 662 Indicates conditions commonly considered in the differential diagnosis of pulmonary-renal s yndrome (diffuse alveolar hemorrhage with glomerulonephritis). Note: conditions causing dif fuse CXR in \201 ltrate and renal failure may mimic these, e.g. severe cardiac failure, se vere pneumonia, leptospirosis. This page intentionally left blank 29 Chapter 6 Diffuse lung disease Causes 30 Clinical assessment and imaging 32 HRCT diagnosis 34 Further investigations 36 CHAPTER 6 Diffuse lung disease 30 Causes Diffuse lung disease is common and its diagnosis is frequently challenging. This cha pter describes a diagnostic approach based on clinical features, imaging, and other investi gations; more detailed descriptions of the dis- eases themselves are presented later in the book. The term \200\230diffuse lung disease \200\231 is used here to describe any widespr ead pulmonary disease process. Patients typically present with breathlessness and bilateral CXR shadowing. The rate of onset and severity of breathlessness are extremely variable, ho wever, and presentations range from an asymptomatic patient with longstanding radiological changes to an acute onset of breathlessness over a period of days, leading rapidly to respi ratory failure and death. Anatomy of diffuse lung disease An understanding of lung anatomy is helpful when considerin g the causes of diffuse lung disease and their appearance on HRCT. Many diffuse lung diseas es primarily affect the interstitium ( \200\230interstitial lung disease \200\231, also des cribed as \200\230diffuse parenchymal lung disease \200\231), a poorly de \201 ned term t hat refers to the connective tissue \201 brous framework of the lung. Centrally, connecti ve tissue surrounds bronchovascular bundles (each consisting of a bronchus and its accompan ying pulmonary artery) that originate at the hila. Peripherally, these connective tissue sh eaths are in continuity with \201 brous interlobular septa, which organize the lung into units called \200\230secondary pulmonary lobules \200\231, polyhedral structures with appr oximately 2-cm sides (see diagram p 817). Interlobular septa, which de \201 ne and separat e secondary pulmonary lobules, contain lymphatics and venules. A secondary pulmonary lobule contains around 5 \200\22312 acini, and is supplied at its center by a bronchiole and pulm onary arteriole. The term \200\230interstitial lung disease \200\231 is confusing because many primarily in terstitial processes also involve the airways, vasculature, and alveolar airspaces. Disease processes that primarily affect the airways (e.g. bron- chiectasis), vessels (e.g. vasculi tis), or airspaces (e.g. pneumonia) may also present with diffuse CXR shadowing and so are included in this chapter. Causes There are several hundred causes of diffuse lung disease, and it is useful to divide these into groups based on their rate of onset and etiology/disease mechanism (see Table 6 .1). Further information Picture of secondary pulmonary lobule, available on-line at: www.vh.org /adult/provider/radiology/ DiffuseLung/AnatImages/2LobuleRadiograph Schema.html British Thoracic Society. BTS guidelines on the diagnosis, assessment and treatment of diff use parenchymal lung disease in adults. Thorax 1999; 54 (suppl. 1): S1 \200\22330 CAUSES 31 Table 6.1. Causes of diffuse lung disease Disease onset Cause/ mechanism Examples (common conditions in bold) Acute (days \200\223 weeks) Infection Bacterial (pneumococcal, staphylococcal, Gram-negative, anaerobic, TB, anaerobic, TB, atypi cal), viral (in \202 uenza, para-in \202 uenza, adenoma, RSV, measles, varicella, hanta), fungal (aspergillosis, histoplasmosis, PCP) Miscellaneous Adult respiratory distress syndrome, acute interstitial pneumonia (AIP), acute hypersensitivity pneumonitis Acute or chronic Drugs Immunosuppressants (methotrexate, azathioprine, cyclophosphamide); treatment of connective tissue disease (gold, penicillamine, sulfasalazine); cytotoxics (chlorambucil, melphalan, b usulfan, lomustine, carmustine, bleomycin, mitomycin); antibiotics (nitrofurantoin, cephalo sporins); anti-arrhythmics (amiodarone); illicit (cocaine inhalation, heroin, methadone, IV talc) Toxins Radiotherapy, high concentration oxygen, paraquat Wegener \200\231s granulomatosis, Churg \200\223Strauss syndrome, Goodpasture \200\231s syn drome, SLE, microscopic polyangiitis, idiopathic haemosiderosis Vasculitis/ alveolar hemorrhage Pulmonary venous hypertension Cardiogenic pulmonary oedema, pulmonary veno-occlusive disease Miscellaneous Sarcoidosis, cryptogenic organizing pneumonia (COP), eosinophilic pneumonia, lipoid pneumon ia Idiopathic interstitial pneumonias Chronic (months \200\223 years) Idiopathic pulmonary \201 brosis (IPF), non-speci \201 c interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), lymphocytic interstitial pneumonia (LIP), respir atory bronchiolitis-associated interstitial lung disease (RB-ILD) Inhalational Inorganic Asbestosis, coal worker s pneumoconiosis, silicosis, metals, e.g. cobalt, aluminum Organic Hypersensitivity pneumonitis, e.g. bird fancier s lung, farmer s lung Connective tissue disease Rheumatoid arthritis, SLE, scleroderma, poly- and dermatomyositis, enclosing spondylitis, S j gren \200\231s syndrome, Beh et \200\231s disease Malignancy Lymphangitis carcinomatosa, bronchoalveolar cell carcinoma, pulmonary lymphoma Miscellaneous Bronchiectasis, Langerhans cell histiocytosis, amyloidosis, lymphangioleiomyomatosis, alveo lar proteinosis, microlithiasis 32 CHAPTER 6 Diffuse lung disease Clinical assessment and imaging History Clinical features may provide useful clues to the u nderlying diag- nosis. Key points in the history are: Presenting symptoms \200 Breathlessness is the most common symptom, and its rate of onset may be useful diagnostical ly (see Table 6.1) Causes of truly episodic breathlessness/diffuse CXR shadowing include eo sinophilic pneumonia, vasculitis, Churg \200\223Strauss syndrome, hypersen- sitivity pneumo nitis, cryptogenic organizing pneumonia, allergic bronchopulmonary aspergillosis, and pulmo nary oedema Cough may occur, although its diagnostic value is uncertain; it may be a promin ent symptom in lymphangitis carcinomatosis, hypersen- sitivity pneumonitis, cryptogenic org anizing pneumonia, sarcoid, and eosinophilic pneumonia. Chronic production of purulent sput um sug- gests bronchiectasis. Bronchorrhoea (production of large volumes of sputum) may occ ur with bronchoalveolar cell carcinoma. Haemoptysis suggests alveolar hemorrhage, malignanc y, or pulmonary venous hypertension Wheeze may occur in asthma associated with eosinophilic pneumonia or Churg \200\223Strauss syndrome Weight loss and fever are non-speci \201 c sy mptoms associated with many diffuse lung diseases. Other medical conditions e.g. malignancy, connective tissue disease, HIV infection, other i mmunosuppression. Ask about old CXRs, which may be helpful in assessing disease duration. Drugs \200 \200 See Table 6.1 for common drug causes of diffuse lung disease Delays of months or even years may occur between starting the drug and developing lung involvement Illicit drug abuse (cr ack cocaine or heroin \200\224pulmonary oedema, eosinophilic pneumonitis, diffuse alveolar hemorrhage, interstitial pneumonia; intravenous drug use \200\224IV talcosis, septic emboli ) Oily nose drops (lipoid pneumonia). Occupation, lifestyle, hobbies, and pets \200 May involve inhalation of inorganic or organic dusts. Document lifelong employment history, including probable exposure levels, use of protective equipment, and names of employers In organic dusts associated with development of diffuse lung disease include asbestos, silica, cobalt, beryllium, aluminum, isocyanates, copper sulfate, iron, tin, barium, and antimony Hypersensitivity pneumonitis may result from inhalation of organic dusts such as Thermoacti nomycetes in moldy hay (farmer s lung), avian proteins or feathers (bird fancier s lung), m ushroom compost, moldy cheese, cork or sugar cane, and isocyanates Risk factors for immunoc ompromise (opportunistic infection, LIP, lymphoma) CLINICAL ASSESSMENT AND IMAGING 33 Smoking history (Langerhans cell histiocytosis, respiratory bronchiolitis- associated inter stitial lung disease, desquamative interstitial pneumonia, and Goodpasture \200\231s syndro me are more common in smokers). Evidence of extrapulmonary disease Manifestations of connective tissue disease, vasculitis, sarcoidosis, e.g. arthralgia, skin rash, ocular symptoms, muscular pain and weakness, Rayn aud \200\231s, nasal/sinus disease, haematuria. Infertility in males (immotile cilia syndro me, cystic \201 brosis). Travel Tuberculosis, pulmonary eosinophilia from parasites (tropics), his- toplasmosis (nor th and central United States, parts of South America and Africa), hydatid disease (Middle E ast, Australasia, Mediterranean). Family history A1-antitrypsin de \201 ciency, rare famil ial forms of UIP and sar- coidosis. Examination \200 \200 \200 Cyanosis and signs of cor pulmonale in severe disease Clubbing (usual interstitial pneumoni tis, asbestosis, bronchiectasis) Basal crackles (usual interstitial pneumonitis, asbestosis , connective tissue disease, pulmonary oedema, lymphangitis, drugs); crackles in bronchiect asis are characteristically coarse Absence of crackles despite a signi \201 cant CXR abnor mality may be suggestive of sarcoidosis, pneumoconiosis, hypersensitivity pneumonitis, or L angerhans cell histiocytosis Squeaks suggest the presence of bronchiolitis Skin, joint, and eye disease (connective tissue disease, sarcoidosis, vasculitis). \200 Imaging CXR is an essential test and is diagnostic in at least 50% of cases. Up to 10% of p atients with biopsy-proven diffuse lung disease have a normal CXR, however. Previous CXRs a re helpful in assessing disease duration and progression. High-resolution CT (HRCT) chest is more sensitive and speci \201 c than CXR for diagnosing diffuse lung disease (see following page and Appendix 4). HRCT is often in itself diagnost ic and should always precede biopsy in the investigation of diffuse lung disease. HRCT also enables assessment of disease extent, and optimal biopsy site if required. HRCT appearance correlates to some extent with disease activity in the interstitial pneu- monias: a predom inantly \200\230ground-glass \200\231 appearance may signify a steroid- responsive in \202 ammatory state, whereas reticulation and honeycombing are often associated with \201 brosis, poor response to treatment, and a worse prognosis. 34 CHAPTER 6 Diffuse lung disease HRCT diagnosis HRCT (and to a limited extent CXR) appearances can be classi \201 ed accord ing to the pattern and distribution of disease, and the presence of additional features (se e also Appendix 4). 1. Imaging pattern Reticular (or linear) pattern Causes include: \200 \200 Interstitial pulmonary oedema Usual interstitial pneumonitis (UIP; reticular shadowing is t ypically patchy, subpleural, and basal; other features include loss of architecture of seco ndary pulmonary lobules, honeycombing, ground-glass change, traction bronchiectasis) Asbest osis (similar features to UIP, often with pleural plaques) Connective tissue disease associ ated \201 brosis (similar features to UIP) Chronic hypersensitivity pneumonitis (often as sociated with regions of ground-glass change, air-trapping on expiration, and centrilobular micronodules) Drug-induced \201 brosis Sarcoidosis. \200 \200 \200 Nodular pattern consists of numerous discrete, round opacities 0.1 \200\2231 cm in diameter . \200 Interstitial processes result in nodularity within interlobular septa, around bronchovascul ar bundles, and subpleurally (e.g. sarcoidosis, which may demonstrate associated perihilar reticular shadowing and lymphadenopathy) Airspace diseases may lead to affected acini becom ing visible as nodules (e.g. hypersensitivity pneumonitis, miliary TB, COP, malignancy).