Pre-existing lung disease The onset of asthma during a dive can be disas- trous and may be provoked by the dry gasses breathed from SCUBA gear (self-contained underwater breathing ap paratus). See BSAC recommendations on asthma and diving (opposite). Many lung diseases, suc h as cystic \201 brosis, COPD (FEV1 <80% predicted), \201 brotic lung disease, previous pneumo- thorax (with no pleurodesis), and lung bullae are considered contraindica- tions t o diving. However, recently, BSAC has adopted the pragmatic approach of accepting that in i ndividuals with a history of spontaneous pneumothorax, who have had no pneumothorax for 5 y ears, the risk of pulmonary baro- trauma is small and not signi \201 cantly greater than f or many in the general population, e.g. smokers. Such individuals may dive provided that a CT scan of the chest and lung function tests (including \202 ow \200\223volume loops) sho w no reason to suggest that there is signi \201 cant residual lung disease. The bends or caisson disease (caisson are underwater air chambers in which people work). Du ring periods of high pressure, extra nitrogen dis- solves into the blood and other tissue \202 uids. This takes many minutes. On ascent this nitrogen literally bubbles off. If the amount coming out of solution is too great, nitrogen bubbles act as emboli and limit blood \202 ow. This produces micro-infarction with activation of in \202 ammatory and clotting cascades and damage to several organs, e.g. joints, spinal cord, brain. Limited diving tim es and slow ascents reduce this problem, as do breathing mixtures containing helium, rather than nitrogen. Severe cases require treatment in hyperbaric chambers. Breath-hold diving During breath-hold diving, increased pressure on the chest elevates alve olar and arterial PO2. This extends breath-hold time, particularly with prior hyperventilat ion to reduce PaCO2. During the dive, DIVING 241 O2 is used and PO2 falls. On ascent, with rarefaction of the thoracic gas, PO2 falls quickl y with possible loss of consciousness and drowning. Pulmonary oedema has been reported whil st SCUBA diving in cold water, but the mechanism is not clear. British Sub Aqua Club (BSAC) recommendations re asthma \200 Asthma may predispose to air-trapping leading to pulmonary barotrauma and air embolism, whi ch may be fatal. An acute asthma attack can also cause severe dyspnoea that may be hazardou s or fatal during diving These theoretical risks should be explained fully to the asthmatic diver. There is little, if any, evidence that the mild controlled, asthmatic that follows the guidelines below is at more risk Asthmatics may dive if they have allergic asthma, but not if they have cold-, exercise-, or emotion-induced asthma All asthmatics should be manag ed in accordance with British Thoracic Society Guidelines Only well-controlled asthmatics m ay dive Asthmatics should not dive if needed a therapeutic bronchodilator in the last 48 h, or have had any other chest symptoms. \200 Control of asthma \200 The asthmatic should not need more than occasional bronchodila- tors, i.e. daily usage woul d be a disqualifying factor, but inhaled steroids/cromoglicate/nedocromil are permissible D uring the diving season he/she should take bd peak \202 ows. A deviation of 10% from best values should exclude diving until within 10% of best values for at least 48 h before divi ng The medical examiner should perform an exercise test such as the 18 in (43 cm) step test for 3 min, or running outside (not a bicycle ergometer) to increase the heart rate to 80% (210 minus age). A decrease in PEFR of 15% at 3 min post-exercise should be taken as eviden ce of exercise-induced bronchoconstriction and, hence, disbars. The patient should be off a ll bronchodilators for 24 h before the test A B2 agonist may be taken pre-diving as a preve ntative, but not to relieve bronchospasm at the time. Further information Aberdeen emergency number for hyperbaric chambers, 07831 151523. www.hy perchamber.com British Thoracic Society guidelines, www.brit-thoracic.org.uk/bts_diving_guidelines_html Diving and medical conditions, www.bsac.org/page/42/medical-matters.htm Diving and pneumothorax, www.bsac.org/page/192/pneumothorax-and-diving.htm Diving, medical forms and certi \201 cates, www.bsac.org/page/100/uk-sdm-forms.htm Plymouth Diving Disease Research Center, www.ddrc.org/docs/contact.htm (24 h help line and reg- ister of hyperbaric chambers) 01752 209999. email enquiries@ddrc.org Cochard G et al. Pulmonary oedema in scuba divers. Undersea Hyperb Med 2005; 32: 39 \200 \22344 This page intentionally left blank 243 Chapter 27 Gastrointestinal disease and the lung Hepatic hydrothorax and hepatopulmonary syndrome 244 Portopulmonary hypertension 246 In \202 ammatory bowel disease, coeliac disease, and pancreatitis 248 244 CHAPTER 27 Gastrointestinal disease and the lung Hepatic hydrothorax and hepatopulmonary syndrome Hepatic hydrothorax Predominantly right-si ded pleural effusion occurring in patients with liver disease and no cardiorespiratory dise ase, often with minimal ascities. The ascitic \202 uid accumulates in the chest as a resu lt of diaphragmatic defects. Occurs in 5 \200\22312% of patients with cirrhosis and portal hypertension. Spontaneous bacterial empyema can occur and is associated with mortality of 2 0%. Diuretics are rarely effective. The de \201 ni- tive treatment is liver transplantatio n. Hepatopulmonary syndrome (HPS) is the triad of: \200 \200 Chronic liver disease and portal hypertension Abnormal intrapulmonary peripheral vascular v asodilatation with decreased pulmonary vascular resistance (right to left shunt) and subseq uent ventilation \200\223perfusion abnormalities Arterial hypoxia. It occurs in 4 \200\22329% of patients with chronic liver disease. The mechanism is thought to be related to the release of vasoactive mediators from portal hypertension causing alte red bowel perfusion, which in turn leads to pulmonary vascular dilatation, with the formati on of vascular spider naevi on the pleura. Patients with cirrhosis who develop hepatopulmon ary syn- drome have a worse prognosis. Presentation is with progressive dyspnoea and cyanosis. Examination reveals clubbing and te langiectasia, with associated stigmata of chronic liver disease. Diagnosis \200 Hypoxia on blood gasses <8.6 kPa on air, at rest and upright. Platypnoea and orthodeoxia ar e present, that is, breathlessness and desaturation on sitting upright, caused by preferent ial perfusion of basal pulmonary vasculature. Lying \202 at relieves this. These changes may be seen in other lung diseases, but in the presence of liver disease is suggestive of H PS. Hypoxia is poorly reversed with 100% oxygen, due to the pulmonary shunting Contrast-enh anced echocardiogram is positive. Contrast/saline bubbles are injected peripherally, and ar e normally seen only in the right heart and are then \201 ltered by the pulmonary bed. In the presence of intrapulmonary shunts, these are seen in the left ventricle. (False- posit ive results occur if right-to-left cardiac shunt present, which can be excluded during echo cardiogram) Pulmonary technetium-99 perfusion scan assesses the shunt fraction. Normally, t he radiolabelled albumin is trapped in the pulmonary capillary bed. In the presence of intr apulmonary or cardiac shunts, there is signi \201 cant uptake of radiolabelled albumin in the brain or spleen. A shunt index fraction of >20% indicates severe hepatopulmonary syndro me CT chest is performed to rule out other pulmonary comorbid disease HEPATIC HYDROTHORAX AND HEPATOPULMONARY SYNDROME 245 Treatment \200 \200 Oxygen if PaO2 <8 kPa Avoid vasodilators. There is minimal evidence for pharmacological int ervention Mainstay of treatment is liver transplantation, which reverses the condition. Hyp oxia may take months to improve. Severe hypoxia (PaO2 <6 kPa) is associated with increased mortality post-transplant, as there is increased risk of hepatic ischaemia Transjugular int rahepatic portosystemic shunt (TIPS) is ineffective Coil embolization can be tried in selec ted cases with AV communications. \200 Prognosis is poor, with a mortality of 40% in 2.5 years. 246 CHAPTER 27 Gastrointestinal disease and the lung Portopulmonary hypertension Portopulmonary hypertension (POPH) is pulmonary artery hyperten sion occurring in association with portal hypertension. It occurs in an estimated 2 \200 \2235% of patients with cirrhosis and is present in around 16% of those referred for liver transplant. The mechanism is unclear, but probably relates to a hyperdynamic circulation, h igh cardiac output, cytokine release, and possible pulmonary emboli. De \201 ned as: \200 Elevated pulmonary artery pressure (>25 mmHg at rest, >30 mmHg during exercise) Increased p ulmonary vascular resistance due to pulmonary vasocon- striction and obliterative vascular remodeling (>120 dyn/s/cm5) Abnormal left ventricular end diastolic/wedge pressure (<15 mmH g) In the setting of portal hypertension (portal pressure >10 mmHg). \200 Presentation Dyspnoea on exertion, possibly syncope, chest pain, fatigue, palpitations, hae moptysis, and orthopnoea. There may be signs of volume overload with raised JVP and pedal o edema. P2 may be loud, with pul- monary and tricuspid regurgitation, as well as stigmata of chronic liver disease. It is usually diagnosed 4 \200\2237 years after the diagnosis of po rtal hypertension. Diagnosis \200 \200 Hypoxia on blood gasses, but less so than in hepatopulmonary syndrome CXR may be normal or show prominent pulmonary arteries and enlarged right heart ECG shows RVH, RBBB, RAD, and si nus tachycardia kCO may be decreased Echocardiography is the main screening test and is dia gnostic if the right ventricular pressure is >50 mmHg Exclude other causes of pulmonary hyp ertension Right heart catheterization with vasodilator studies is performed The changes in the vessels in POPH are the same histologically as those seen in IPAH (see p 388). \200 \200 \200 \200 Treatment Options are the same as for patients with IPAH, with vasodi la- tors, prostacycli n, and endothelin antagonists (see p 394). Avoid B-blockers, so manage varices with banding . Anticoagulation is not advised due to the risk of variceal bleeding. LTOT if PaO2 <8 kPa. Liver transplantation may reverse mild to moderate POPH, although symptoms may take weeks to months to resolve. Severe POPH is not reversed and is asso- ciated with signi \201 cant intra- and post-operative morbidity and mortality. A few cases of heart \200\223lung \200 \223liver transplants have been reported. Prognosis is poor in severe POPH, with a median survival after diagnosis of 6 months, witho ut transplant. PORTOPULMONARY HYPERTENSION 247 Further information Hoeper M et al. Portopulmonary hypertension and hepatopulmonary syndrom e. Lancet 2004; 363: 1461 \200\2238 Budhiraja R, Hassoun P. Portopulmonary hypertension. A tale of two circulations. Chest 2003 ; 123: 562 \200\22376 248 CHAPTER 27 Gastrointestinal disease and the lung In \202 ammatory bowel disease, coeliac disease, and pancreatitis In \202 ammatory bowel disease (IBD) Pulmonary involvement tends to occur after the onset of the IBD, but can pred ate it. Pulmonary involve- ment is found in up to a fourth of patients, but this is usually subclinical. Patients can develop a variety of clinical syndromes, including airway in \202 ammation, subglottic stenosis, chronic bronchitis, bronchiectasis, and chronic bronchi olitis. Bronchoscopy may reveal in \202 ammatory tissue within the large airway walls, whi ch on biopsy shows mucosal ulceration, basal cell hyperplasia, basement membrane thickening , and submucosal in \202 ammatory cell in \201 ltration. IBD is also associated with the development of interstitial lung disease, such as cryptogenic organizing pneumonia (COP), p ulmonary in \201 ltrates with eosinophilia, or neutrophilic necrotic parenchymal nodules. Pulmonary involvement tends to be steroid-responsive. Inhaled steroids can be tried for chr onic bronchitis, but oral or intravenous steroids may be required for worsening lung involv ement. Note that drugs used in the treatment of IBD may also cause lung disease, such as su lfasalazine (alveolitis), mesalazine, or in \202 iximab (both: pulmonary in \201 ltrates and eosinophilia; in \202 iximab: reactivation of latent TB). Ulcerative colitis Pulmonary involvement is usually asymptomatic or may be associated with dry cough. Minimal interstit ial change may be suggested by abnormal pulmonary function tests. Restrictive, obstructive, or reduced kCO defects may be seen. Usually normal CXR and CT. No speci \201 c treat- men t indicated. Crohn \200\231s disease Pulmonary involvement less common than in ulcerative c olitis, but similar changes found. Coeliac disease May be associated with idiopathic lung \201 brosis, causing restrictive defect. Also may be at increased risk of asthma, bird fan cier \200\231s lung, and haemosiderosis. Increased risk of lymphoma and malignancy in GI tr act. Pancreatitis Acute pancreatitis is frequently associated with exudative pleural effusi on. Raised amylase in the pleural \202 uid is suggestive (see p 55). Adult respiratory di stress syndrome (ARDS) may develop, which requires supportive care and mechanical ventilati on (see p 101). Further information Mahadeva et al. Clinical and radiological characteristics of lung disea se in in \202 ammatory bowel disease. Eur Respir J 2000; 15: 41 \200\2238 249 Chapter 28 Hypersensitivity pneumonitis Causes 250 Diagnosis 252 Management 254 250 CHAPTER 28 Hypersensitivity pneumonitis Causes De \201 nition Group of lung diseases caused by inhalation of organic antigen to wh ich the individual has been previously sensitized. Hypersensitivity pneumonitis (HP; previo usly termed extrinsic allergic alveolitis) is often divided into \200\230acute \200\231 an d \200\230chronic \200\231 forms based on the time-course of pres- entation. Acute HP ofte n follows a short period of exposure to a high concentration of antigen, and is usually rev ersible. Chronic HP typically follows a period of chronic exposure to a low antigen dose an d is less reversible. These two presentations may overlap and \200\230subacute \200\231 fo rms of the disease are recognized. Epidemiology Exact prevalence unknown. At least 8% of bu dgerigar and pigeon keepers and up to 5% of farmers may develop HP. Hypersensitivity pneumo nitis is thought to be more common in non-smokers (mechanism unclear; may re \202 ect inhi bition of alveolar macrophage function by smoke). Causes Many different antigens have been reported to cause HP, ranging from the relatively common (bird-fancier \200\231s lung and f armer \200\231s lung in the UK; summer-house HP in Japan) to the more unusual and exotic (s hell lung \200\224proteins on mollusc shells; pituitary snuff-taker \200\231s disease; seri cul- turist \200\231s lung \200\224silk worm larvae proteins; sax lung \200\224yeast on sax ophone mouthpieces). Important examples are listed in Table 28.1. Table 28.1 Causes of hypersensitivity pneumonitis \200\224examples Antigen Sources Diseases Organisms Farmer s lung; bagassosis; compost lung; mushroom worker s lung; humidi \201 er lung Moldy hay; sugarcane; compost; mushrooms; contaminated water in humidi \201 ers and air co nditioners Thermophilic actinomycetes (Micropolyspora faeni, Thermoactinomyces vulgaris), Aspergillus spp Aspergillus clavatus Moldy barley Malt worker s lung Trichosporon cutaneum House dust Summer-house HP (Japan) Cladosporium spp Ceiling mold Hot tub lung Animal protein Bird proteins Bloom on bird feathers and droppings Bird fancier \200\231s lung Rat proteins Rat droppings Rat lung Chemical Toluene diisocyanate Paints Isocyanate HP CAUSES 251 Pathophysiology Pathogenesis of HP is not fully understood, and may involve T-cell mediated immunity and granuloma formation (type IV hyper- sensitivity) and/or antibody \200\223anti gen immune complex formation (type III hypersensitivity). It is not an atopic disease, and is not characterized by a rise in tissue eosinophils or IgE (type I hypersensitivity); this may, in part, be due to the small particle size of offending antigens, which tend to be de posited more distally in the air-spaces than the larger particles associated with asthma. L ung histology specimens typically reveal an inter- stitial in \202 ammatory in \201 ltrat e, often with accompanying bronchiolitis and organizing pneumonia. Non-caseating granulomat a are often present, and typically are ill-de \201 ned and single (cf. sarcoidosis, where granulomata are well-de \201 ned and are grouped subpleurally or near bronchi). Chronic HP is characterized by \201 brosis, and often the absence of granulomata and airways involv ement, particularly if antigen exposure has ceased. 252 CHAPTER 28 Hypersensitivity pneumonitis Diagnosis Clinical features Acute HP \200 Breathlessness, dry cough, and systemic symptoms (fever, chills, arthralgia, myalgia, heada che) occur 4 \200\2238 h after exposure to antigen Examination: crackles and squeaks on aus cultation, fever In the absence of ongoing exposure, symptoms settle spontaneously within 1 \200\2233 days. Episodes may be recurrent. \200 Chronic HP \200 Progressive exertional breathlessness, dry cough, sometimes systemic symptoms (weight loss) over the course of months \200\223years. May be history of acute episodes Examination: cra ckles and squeaks on auscultation, clubbing rare, may be features of cor pulmonale. Investigations \200 Imaging: acute HP \200 CXR Diffuse small (1 \200\2233 mm) nodules or in \201 ltrates, sometimes ground glass chan ge, apical sparing. Normal in up to 20% of cases HRCT Patchy ground-glass change and poorly de \201 ned nodules. Areas of increased lucency (enhanced on expiratory HRCT) occur due t o air trapping from bronchiolar involvement Both CXR and HRCT appearances may quickly norma lize following removal from antigen exposure Imaging: chronic HP \200 \200 CXR Typically upper- and mid-zone reticulation HRCT Diffuse well-de \201 ned centrilobular nodules, ground-glass change, increased lucency from air trapping. May mimic IPF PFTs Typically restrictive pattern with reduced gas transfer and lung volumes; mild obstruc tion is also sometimes observed. Hypoxia may occur Bloods Acute hypersensitivity pneumoniti s associated with neutrophilia but not eosinophilia. In \202 ammatory markers often increa sed Serum antibody (IgG) precipitin results are presented either as an ELISA or as a number of precipitin lines, referring to the number of different epitopes an individual responds to. Precipitins to organic antigens are found in 90% of patients, but are also present in u p to 10% of asymptomatic farmers and 50% of pigeon breeders. Precipitin levels often fall i n the absence of ongoing antigen exposure BAL lymphocytosis (>40% of cells) is a typical \201 nding, but not in itself diagnostic Transbronchial or surgical lung biopsy may be requ ired in cases of diagnostic uncertainty. TBB may provide insuf \201 cient tissue for adequ ate histological analysis Inhalation antigen challenge may be unpleasant, and is not recomm ended routinely DIAGNOSIS 253 Diagnosis is based on the combination of history of antigen exposure and typical clinical a nd HRCT features. The most diagnostically useful clinical features are an onset of symptoms 4 \200\2238 h after exposure, a history of recurrent episodes of symptoms, the presence of weight loss, and the \201 nding of crackles on examination. An absence of serum precipit ins is very unusual but described. Atypical presentations require further investiga- tion t o support the diagnosis, such as BAL lymphocytosis or characteristic histological features on lung biopsy. Differential diagnosis \200 Atypical pneumonia \200 Idiopathic interstitial pneumonias (particularly IPF and COP) \200 Sarcoidosis \200 Vasculitis \200 Occupational asthma (e.g. from isocyanates) \200 Drug-induced lung disease (including pesticides) \200 Orga nic dust toxic syndrome (follows very high levels of exposure to agricultural dusts, sympto ms transient, benign course) Silo- \201 ller \200\231s disease (variable respiratory manif estations following exposure to nitrogen dioxide in silos; ranges from mild bronchitis to f atal bronchospasm) 254 CHAPTER 28 Hypersensitivity pneumonitis Management Management centers on antigen avoidance, which is frequently dif \201 cult. If complete removal from antigen is unrealistic (e.g. farmers), measures to reduce exposure ma y be of bene \201 t (such as respiratory protection with high performance, positive pressu re masks; avoidance of particularly heavy exposure; improved ventilation and use of air \201 lters; drying of hay prior to storage). In acute HP, symptoms typically resolve following cessation of antigen exposure and treatme nt is usually not required. Removal from exposure may also result in symptomatic and physio logical improvement in chronic HP, although this is less certain and established pulmonary \201 brosis is often irreversible. When treatment is required, corticosteroids are frequently used although there is a lack of randomized controlled evidence to support this. Steroids may hasten the resolution of impa ired pulmonary function in acute HP, although their effect on long-term outcome is unclear. A typical regimen is prednisolone 40 \200\22360 mg daily for up to a month, and then slowl y reduce dose over several months. Inhaled steroids have not been studied in detail, althou gh may be of some bene \201 t. Prognosis Highly variable. Prognosis is usually excellent f ollowing removal from antigen exposure in acute HP, although progression to respi- ratory f ailure and death may very rarely occur after short-term exposures of very high intensity. R ecurrent episodes of acute HP do not necessarily progress to chronic HP and \201 brosis, and chronic HP may develop in the absence of previous acute HP episodes. Development of chr onic HP with ongoing exposure may eventually lead to cor pulmonale and death, although agai n this is variable and many patients do not exhibit disease progression despite chronic exp osure. Persistent low-dose exposure (e.g. budgerigar in the house) may be more likely to pr ogress to the chronic \201 brotic form of HP than intermittent high-dose exposure (e.g. p igeon fanciers), which predisposes more to episodes of acute HP. Further information Schuyler M. Hypersensitivity pneumonitis, Lesson 6, Volume 14 in PCCU E ducation Series online at www.chestnet 255 Chapter 29 Hyperventilation syndrome 256 CHAPTER 29 Hyperventilation syndrome De \201 nition Poorly de \201 ned, and the term is falling into disfavor, dysfunc- tional breathing being the alternative. Most respiratory physicians still use hyperventilation sy ndrome to describe breathlessness and over-breathing associated with fear, stress, and anxi ety, in the absence of any demon- strable physiological abnormality. Usually part of a spectrum of physical symptoms (e.g. chest pain, palpitations/tachycardia, fatigue, dizziness, parasthesiae, headache, diarrhea, inappropriate sweating, etc.) from a n anxiety or panic disorder. Other specialties may have been consulted due to the mixed sym ptomatology. Pathophysiology Hyperventilation syndrome can occur de novo, or follow a respi ratory disorder that has resolved \200\224such as an attack of mild asthma. It appears to b e based on a heightened awareness of breathing, and concerns as to what the shortness of br eath signi \201 es. The PaCO2 is inter- mittently low, with a respiratory alkalosis. Recor dings of breathing pattern often show a rather chaotic pattern. Clinical features \200 Intermittent episodes of breathlessness largely unrelated to exercise, although can be wors ened by exercise May be associated with symptoms of respiratory alkalosis, such as numbness , tingling of the extremities, feelings of impending doom, and light-headedness, occasional ly to the point of losing consciousness (cerebral vasoconstriction due to the hypocapnia) S ensation of not being able to take a satisfactory breath No history suggestive of an altern ative current respiratory disorder, although there may have been one previously History of some stressful situation in the patient \200\231s life Previous episodes. \200 \200 Diagnosis is essentially one of exclusion, but with additional con \201 rma- tory \201 n dings. \200 \200 No evidence of a cardiac cause for the breathlessness No evidence of a respiratory cause, i .e. normal lung function, normal CXR, and normal SaO2 at rest and on exercise to the point of breath- lessness (SaO2 may even rise on exercise) Irregular breathing pattern at rest an d on exercise No evidence of pulmonary hypertension No evidence to support pulmonary emboli No evidence of hyperthyroidism Low PaCO2, raised pH, on blood gasses (and a normal A \200 \223a gradient) No metabolic acidosis on blood gasses (e.g. ketoacidosis, lactacidosis) Unr esolved psychological issues, or social phobia/agoraphobia. \200 \200 \200 \200 \200 \200 HYPERVENTILATION SYNDROME 257 Differential diagnosis Important pathological causes to exclude are: \200 Subtle intersti tial lung disease with a normal CXR: consider HRCT \200 Mild asthma with normal basic PFT s: consider PEFR monitoring, exer- cise provocation, or bronchial reactivity testing Pulmon ary hypertension/thromboembolic disease: consider cardiac echo or CTPA Hyperthyroidism Unex pected acidosis: e.g. renal failure, lactacidosis, ketoacidosis. \200 Management It is important not to dismiss the patient \200\231s symptoms, implying it is \200\230all in the mind \200\231. The patient has a real symptom, which requires a real exp lanation. There are no controlled trials of management, but most clinicians will offer an e xplanation based on an \200\230over-awareness \200\231 of respiratory sensations, heighten ed by anxiety. It is important to explain that the associated symptoms of tingling and ligh t-headedness are well recognized and harmless. Old recommendations to rebreathe into a paper bag have not stood the test of time and are r ather impractical in the middle of a supermarket. Because cold peripheries often accompany an episode (vasoconstriction), placing the cold palms on to the cheeks can help suppress th e desire to breathe, thought to be related to the diving re \202 ex: again, this is an unt ested remedy. Careful explanation may be enough. A short period on an anxiolytic (e.g. diazepam 2 \200 \2235 mg bd) may be helpful, to demonstrate that the symp- toms can be controlled. Manageme nt of the psychological problem may be possible. Some experienced respiratory physiotherapi sts can help patients control their symptoms and divert the anxiety away from breathing. Failure to respond should always prompt a reconsideration of whether an underlying disorder is gradually progressing to the point where an inves- tigation becomes abnormal. On the ot her hand, repeated investigations will con \201 rm the patient \200\231s concern that the doctors think there is something wrong. \200\231 Prognosis Some patients improve quickly w ith explanation. Some tend to relapse at times of stress. Some prove resistant to any treat ment and probably should be seen in the clinic regularly, but infrequently, to reduce their likelihood of involving other medical services with another pointless round of investigati ons. 258 CHAPTER 29 Hyperventilation syndrome Nijmegen hyperventilation score (Table 29.1) Filled in by a patient; a score of 22 or over is highly suggestive of hyperventilation syndrome. Table 29.1 Example of Nijmeqen hyperventilation score Before treatment Never 0 Rare 1 Some- times 2 Often 3 Very often 4 Chest pain \234\223 Feeling tense \234\223 Blurred vision \234\223 Dizzy spells \234\223 Feeling confused \234\223 Faster/deeper breathing \234\223 Shortness of breath \234\223 Tight feeling in the chest \234\223 Bloated feeling in the stomach \234\223 Tingling \201 ngers \234\223 Unable to breath deeply \234\223 Stiff \201 ngers or arms \234\223 Tight feeling around mouth \234\223 Cold hands or feet \234\223 Heart racing (palpitations) \234\223 Feeling anxious \234\223 Total score 34 259 Chapter 30 Idiopathic interstitial pneumonias Overview 260 Idiopathic pulmonary \201 brosis (IPF): diagnosis 262 IPF: management 1 264 IPF: management 2 266 Non-speci \201 c interstitial pneumonia (NSIP) 268 Cryptogenic organ izing pneumonia (COP) 270 Acute interstitial pneumonia (AIP) 272 Respiratory bronchiolitis- associated interstitial lung disease (RB-ILD) 274 Desquamative interstitial pneumonia (DIP) 276 Lymphoid interstitial pneumonia (LIP) 278 260 CHAPTER 30 Idiopathic interstitial pneumonias Overview De \201 nition The IIPs comprise a group of diffuse lung diseases of unknown etio logy that primarily involve the pulmonary interstitium \200\224 the area between the alveol ar epithelium and capillary endothelium, as well as the septal and bronchovascular tissues that make up the \201 brous framework of the lung. These primarily interstitial processes , however, also frequently involve the airways, vasculature, and alveolar airspaces. The un derlying pathological process is one of varying degrees of in \202 ammation and \201 bro sis. The terminology used to describe the IIPs may be confusing; these conditions have been subj ect to much reclassi \201 cation, re \202 ecting the lack of understanding of their under lying etiology and pathogenesis. Idiopathic pulmonary \201 brosis (IPF; previously termed cryptogenic \201 brosing alveolitis) is the commonest IIP and is characterized by the hi stological pattern of usual interstitial pneumonia (UIP). The other IIPs are distinct disea se enti- ties and are all rare. They all represent a subgroup of interstitial (or diffuse p arenchymal) lung diseases. Diagnosis Made from a combination of clinical, HRCT, and histolo gical features \200\224distinguish from other causes of diffuse lung disease (see Chapter 6 ). Histological patterns are the most speci \201 c and form the basis for the current clas si \201 cation of IIPs. Surgical lung biopsy is recommended for most cases of suspected II P with the exception of patients exhibiting typical clinical and HRCT features of IPF. Tran sbronchial biopsies have a very limited role due to the generally patchy distribution of th e IIPs, although they may be useful in the diagnosis of acute interstitial pneumo- nitis (A IP) and cryptogenic organizing pneumonia (COP), as well as the exclusion of other causes of diffuse lung disease (e.g. sarcoidosis). Treatment The optimal treatment of many of the II Ps is poorly estab- lished, and there is a lack of supportive data from randomized controll ed trials. Steroids and immunosuppression are the mainstay of treatment, but these are ofte n ineffective and have signi \201 cant side-effects. Treatment may alter both the HRCT and histological pictures, and if possible should be delayed until a diagnosis has been made. The conditions currently included within the classi \201 cation of idiopathic interstitial pneumonias, together with their key clinical, imaging, and his- tological features and pro gnosis, are presented in Table 30.1 opposite and discussed in detail in the remainder of th is chapter. They are listed in order of frequency. Further information ATS/ERS. International Multidisciplinary Consensus Classi \201 cation of the Idiopathic Interstitial Pneumonias. Am J Resp Crit Care Med 2002; 165: 277 \200\2233 04 OVERVIEW 261 Table 30.1. Idiopathic interstitial pneumonias: summary of key features Idiopathic pulmonar y \201 brosis (IPF) [previously cryptogenic \201 brosing alveolitis (CFA)] Idiopathic Onset over years HRCT \201 brosis, honeycombing, minimal ground glass, subpleu ral, and basal distribution Histology usual interstitial pneumonia (UIP): areas of intersti tial \201 brosis (made up of foci of proliferating \201 broblasts) interspersed with no rmal lung (temporal and spatial heterogeneity), minimal in \202 ammation Prognosis poor Non-speci \201 c interstitial pneumonia (NSIP) Idiopathic or disease-associated Onset over months \200\223years HRCT diffuse ground glass, \201 ne reticulation, minimal honeycombing Histology varying degrees of in \202 ammatio n and \201 brosis, more uniform appearance than UIP Prognosis variable, can be good Idiopathic or disease-associated Onset over months HRCT areas of consolidation, basal, subp leural, and peribronchial predominance Histology alveolar spaces \200\230plugged \200\231 with granulation tissue, extension into bronchioles Prognosis generally good Cryptogenic organizing pneumonia (COP) [previously idiopathic bronchiolitis obliterans orga nizing pneumonia, BOOP] Acute interstitial pneumonia (AIP) Idiopathic Many similarities to ARDS Onset over days HRCT diffuse ground glass and patchy c onsolidation Histology diffuse alveolar damage: interstitial oedema, intra-alveolar hyaline membranes, followed by \201 broblast proliferation and interstitial \201 brosis Progno sis poor Idiopathic, occurs in smokers Onset over years Symptoms usually mild HRCT centrilobular nod ules, ground glass, thick-walled airways Histology pigmented macrophages in bronchioles Pro gnosis good Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) Desquamative interstitial pneumonia (DIP) Idiopathic, occurs in smokers Onset over weeks \200\223months HRCT ground glass Histology p igmented macrophages in alveolar air spaces (perhaps a more extensive form of RB-ILD), temp orally uniform appearance Prognosis good Lymphoid interstitial pneumonia (LIP) Idiopathic or disease-associated Onset over years HRCT ground glass, often reticulation His tology diffuse interstitial lymphoid in \201 ltrates Prognosis variable 262 CHAPTER 30 Idiopathic interstitial pneumonias Idiopathic pulmonary \201 brosis (IPF): diagnosis De \201 nition Chronic interstitial pn eumonia of unknown cause charac- terized histologically by temporal and spatial heterogenei ty, with areas of \201 brosis and architectural distortion interspersed with areas of nor mal lung. This occurs as different areas of lung are in varying stages of evolu- tion of th e pathological process. The histological appearance of idiopathic pulmonary \201 brosis ( previously known as cryptogenic \201 brosing alveolitis) is usual interstitial pneumonia (UIP). Epidemiology Prevalence \201 gures vary from 6 to 14/100 000, although prevalence may be 175/100 000 in patients >75 years old. Slightly more common in males. Mean age at pr esentation 67. Familial form well described, but very rare. Causes and pathophysiology The development of \201 brosis was previ- ously thought to re \202 ect a response to chronic in \202 ammation resulting from an unknown initial injury. This key role of in \202 amma tion in the pathogenesis of IPF has been questioned, however, based partly on the observati ons that in \202 ammation is not a major feature of pathological specimens, and that respo nses to \200\230anti-in \202 ammatory \200\231 treatment with steroids are often poor. An alternative theory is that repeated alveolar epithelial injury leads directly to wound hea ling and \201 brosis, and this concept of \200\230 \201 brosis without in \202 ammatio n \200\231 has been demonstrated both in animal models and other human diseases. The nature of the lung injury remains obscure: postulated triggers include inhalation of metal dust a nd wood dust, smoking, or expo- sure to the Epstein \200\223Barr virus. Cytokine production (e.g. plasminogen acti- vator inhibitors, matrix metalloproteinases, transforming growth f actor B) by alveolar epithelial cells may play an important role in the development of \201 brosis. Host genetic factors are also likely to be important in modi- fying the wound- healing response. Clinical features \200 Typically presents with gradual onset exertional breathlessness and cough; average of 9 mon ths of symptoms prior to presentation 5% of patients are said to be asymptomatic, although this is likely to be an underestimate Arthralgia occurs in about 20% Fine basal late inspir atory crackles Clubbing in up to 50% Cyanosis and cor pulmonale in severe disease. \200 \200 \200 Investigations \200 Blood tests Raised ESR and CRP and mild anemia may occur; positive rheumatoid factor and/or ANA may occur at low titres in the absence of associated connective tissue disease PFTs Ty pically restrictive pattern with reduced vital capacity and transfer factor; smokers may ex hibit coexisting obstructive defect. Oxygen saturations are frequently reduced, particularl y on exertion; ABGs may demonstrate type I respiratory failure IPF: DIAGNOSIS 263 CXR Peripheral and basal reticular shadowing, may extend to other zones, sometimes with hon eycombing; rarely may be normal HRCT features include bilateral, peripheral, and subpleural reticulation, with honeycombing, traction bronchiectasis, architectural distortion, and mi nimal or no ground-glass change. Predominantly basal initially, more extensive later in dis ease course. Extent of disease on CT corre- lates with physiological impairment. Predominan t ground-glass appear- ance suggests an IIP other than IPF \200\224consider lung biopsy BAL is not routinely required and is rarely helpful. Typically shows neu- trophilia, sometimes mild eosinophilia. Marked eosinophilia (>20%) or lymphocytosis (>50%) should raise possibi lity of alternative diagnosis Lung biopsy (via VATS or thoracotomy) if there is diagnostic doubt Gallium and DTPA scanning are seldom of use in clinical practice. \200 Histology Usual interstitial pneumonia, a \201 brosing pattern character- ized by tempora l and spatial heterogeneity: patches of active \201 broblastic foci (re \202 ecting acut e injury) are interspersed with honeycombing/archi- tectural distortion (re \202 ecting ch ronic scarring) and areas of normal lung, re \202 ecting varying stages of evolution of th e disease process in different areas of lung. Interstitial in \202 ammation is minimal. Si gni \201 cant inter-observer disagreement between expert pathologists regarding the presen ce of a UIP pattern on lung biopsy has been reported, however, and an overall diagnosis tak ing into account clinical, radiological and histological features is recommended. Diagnosis can be con \201 dently made in most cases on the basis of clinical and HRCT \201 ndings . Lung biopsy is not generally required in patients with typical clinical and HRCT features of IPF, but should be considered in the presence of unusual features (e.g. predominant gro und glass/nodules/ consolidation/upper lobe involvement on HRCT, or young patient). When re quired, biopsies should be obtained at VATS or thoracotomy; transbron- chial biopsies provi de smaller samples, which rarely give diagnostic infor- mation due to the patchy distributi on of disease. Differential diagnosis \200 