pancreatic enzyme preparations have been found to be associated with the development of col onic strictures, or \201 brosing colonopathy; hence maximum levels of lipase of 10 000 un its/kg/day have been recommended Vitamins Fat-soluble vitamins are not absorbed well in pat ients with CF and these need replacement. Vitamins A, D, and E should be started when pancr eatic insuf \201 ciency is diagnosed and vitamin K if there is evidence of liver disease, with prolonged prothrombin time. Vitamins should be taken at meal times with pancreatin. Vi tamin levels should be checked at annual review Salt tablets in hot weather, due to excessi ve losses in sweat. Gastrointestinal disease \200 Distal intestinal obstructive syndrome (DIOS)/abdominal pain (meconium ileus equivalent). B loating, abdominal pain, possible pal- pable caecal mass, and complete or incomplete intest inal obstruction. Abdominal X-ray shows empty colon and ileal distension with air- \202 ui d levels. Occurs secondary to dehydration, or rapidly increased doses of pancreatic enzymes . Rarely needs surgery. Medical treatment with senna and oral acetylcysteine 200 mg tds and gastrogra \201 n 50 \200\223100 mL tds for 5 days is usually adequate. If not, perform gastrogra \201 n enema to determine site of obstruction. This can be therapeutic. Oral i ntes- tinal lavage with Kleen Prep solution and up to 10 L of \202 uid over 1 \200\2232 days can also be given. The treatment is considered to have worked when \202 uid is pass ed from the rectum and symptoms have resolved. If not resolving, may need further imaging t o rule out intussusception Re \202 ux More common in patients with CF than the general pop ulation. Symptoms may occur during physiotherapy, which require changes to positioning/tipp ing. May require treatment with a proton pump inhibitor to prevent development of Barrett \200\231s esophagus Pancreatitis Can occur in those patients who are pancreas-suf \201 cie nt. Seen in up to 15% adults with CF. May present as severe acute attack or chronic recurre nt abdominal pain. Not usually as unwell as NON-PULMONARY DISEASE 223 non-CF patients with pancreatitis. Raised amylase and abnormal USS/ CT. Treat with bowel re st, protein pump inhibitor, IV rehydration. Liver and biliary disease \200 Liver screening \200\224cirrhosis, portal hypertension Reduced bile production and deranged bile acid composition leads to biliary obstruction, portal tract in \202 ammation, and ev entual \201 brosis and focal biliary cirrhosis. Cirrhosis affects 2 \200\22325% of CF pat ients. Annual screening liver USS is performed, as blood tests can be unhelpful (although A LP most sensitive). Biopsy unhelpful as patchy disease. Established cirrhosis can lead to v ariceal bleeds, so annual screening endoscopies are performed in those with cirrhosis. Cirr hosis may need treatment with ursodeoxycholic acid, porto- systemic shunts, and sclerothera py. Liver transplant may be necessary. Metabolic disease \200 CF-related diabetes (CFRD) is becoming increasingly common as the median age of survival wi th CF increases. Pancreatic damage in CF (due to \201 brosis) causes decreased insulin se cretion. Approximately 50% of 30-year-olds will have CFRD. Presents insidiously and non-spe ci \201 cally, with weight loss or fall in lung function, and not with ketoacidosis. Scree ning glucose tolerance test or random/fasting glucose should be performed annually and more frequently in those on overnight enteral feeds or those with clinical symptoms suggestive of diabetes. Once dia- betes is diagnosed, patients should not be managed on a hypoglycaemi c diet. Lower doses of insulin are usually required than in IDDM. There is no indication fo r oral hypoglycaemics. Microvascular complications can occur and annual screening for these should be performed Osteoporosis Several studies have con \201 rmed an increased incidenc e of low bone mass in CF and increased fracture risk, particularly ribs. Risk factors inclu de malabsorption of vitamin D and calcium, low body mass index, decreased physical activity , delayed puberty, steroid use, diabetes. Treatment is with calcium and vitamin D supplemen ts to maintain vitamin D levels, weight-bearing exercises, hormones for delayed puberty (et hinylestradiol or testosterone), bisphosphonates. Other organ systems \200 Arthropathy and CF vasculitis Acute or subacute arthritis occurs in around 5% of patients w ith CF. It often responds to NSAIDs. Sometimes arthritis is associated with skin lesions, s uch as purpura or erythema nodosum. Up to 40% may be ANCA positive. Purpuric vasculitis is associated with more severe lung disease Nasal polyps and sinusitis Nasal polyps occur in 3 0% and can cause nasal obstruction. Treatment with topical or systemic steroids and deconge stants is usually not helpful and polypectomy may be required, often more than once. Asympt omatic sinusitis is common and can cause mucosal swelling. Consider sinus CT if problematic Stress incontinence occurs in both men and women, caused by coughing. It has been recogniz ed as an increasing problem. Pelvic \202 oor exercises can be taught by physiotherapists. 224 CHAPTER 24 Cystic \201 brosis Other issues Fertility Women with CF are usually subfertile. When planning a pregnancy, their physical state shoul d be optimized with antibiotics and nutrition. The outcome of a pregnancy is improved by op timizing and maintaining pul- monary function and weight gain during the pregnancy. Close m onitoring throughout is required. Pregnancy does not affect survival when compared with the entire adult female CF population, but impaired pulmonary func- tion with FEV1<60% predict ed is likely to be the main predictor of worse maternal and fetal outcome. Breast-feeding i s possible, but intensi \201 es the nutritional strain put on the mother. Most CF antibiot ics are safe to use in pregnancy, but avoid cipro \202 oxacin, chloramphenicol, metronidaz ole, and IV colistin. Care with aminoglycoside levels. Men are infertile due to failure of the normal development or blockage of the vas deferens, seminal vesicle, ejaculatory duct, and body and tail of epididymis. Testicular histology i s normal and hence one option is surgical sperm retrieval for intracytoplasmic sperm inject ion (ICSI) into an egg, performed by fertility clinics. Genetic counseling and screening sh ould be offered to patients with CF and their partners. Psychosocial support Trained psycho logists offer personal and family support regarding education, employment, \201 nancial b ene \201 ts, burden of treatment, and adapting to progressive disease. Pre-transplant psyc holog- ical assessment is carried out, as well as terminal care and bereavement counseling. Also treat depression, anxiety, and emotional dif \201 culties, with referral to psychiat ric services if necessary. Social worker involvement to help with bene \201 t entitlements , travel insurance, disabled car badge. Care of the dying CF patient When all acknowledge t hat there are no further treatment options, the focus of care should adjust to being pal- l iative, with an emphasis on symptom relief, at home or in hospital. Future developments Gen e therapy. Replacing CFTR function to prevent progressive airways disease. Work is focusing on \201 nding a suitable vector for delivery, such as nebulizer and airway epithelial im plantation. Progress so far has been disappointing, but work is ongoing. Further information CF Trust.Standards for the clinical care of children and adults with cy stic \201 brosis in the UK 2001. www.cff.org (USA) www.cftrust.org.uk, www.cystic \201 brosis.co.uk (both UK) CF mutation database: www.genet.sickkids.on.ca This page intentionally left blank 226 CHAPTER 24 Cystic \201 brosis Seeing the patient with CF in clinic Routine visit \200 Fill in paperwork for UK CF database (now called PORT CF) \200\224contains basic data such as height, weight, oxygen saturation, number of hospital admissions, and details of antibio tic use, as well as regular medications Check spirometry, weight, oxygen saturation Antibio tics if required \200 At the annual review \200 Fill in paperwork for UK CF database (now PORT CF) \200\224contains basic data such as heig ht, weight, number of days off school/work, number of complications, antibiotic use, organi sms cultured, supplemental feeding, fertility, glucose level, transplant status, and treatm ent compliance Weight Height (until they stop growing) Radiology \200 \200 \200 CXR (calculate the Northern score; see CF annual review documentation) Liver and biliary sy stem USS (Doppler if known cirrhosis) Bloods \200 \200 \200 \200 \200 \200 \200 Sputum \200 \200 Physiotherapy review Exercise testing (6-min walk test or shuttle walk test) Respiratory function \200 \200 \200 Dietician \200 CF nurse review Psychologist review Social worker review Doc tor review FBC and clotting studies U&E, LFTs Fasting glucose tolerance test HbA1c if established diab etes Aspergillus species RAST and precipitins IgA, IgG, IgM, and IgE Fat-soluble vitamin le vels A, D, E, and K, if available M, C&S including B. cepacia, S. aureus, Aspergillus, and MRSA NTM \200 \200 Spirometry Oximetry and, if <92%, blood gas KCO, lung volumes Full assessment and review of dietary intake, enzyme and vitamin use \200 \200 \200 227 Chapter 25 Eosinophilic lung disease Eosinophilic lung disease 228 Causes of eosinophilic lung disease 1 230 Causes of eosinophi lic lung disease 2 232 228 CHAPTER 25 Eosinophilic lung disease Eosinophilic lung disease De \201 nition Pulmonary eosinophilias are disorders classically associated with CXR in \201 ltrates and a raised blood eosinophil count, although eosi- n ophilic in \201 ltration of the lung can occur without blood eosinophilia. \200 Eosinophils are phagocytes that are produced in bone marrow and circulate for up to 10 h be fore localizing in tissues Their blood levels are usually tightly regulated In health they accumulate in the GI tract mucosa, but they may be attracted to other tissues by chemoattra ctant mechanisms, including mast cell activation and complement activation Eosinophils can survive in the tissues for weeks if appropriate cytokines are present Persisting high eosin ophil levels cause tissue damage, due to their pro-in \202 ammatory effects Eosinophils ac cumulate in allergic or hypersensitivity disease, parasitic infections, and cancer Steroids and severe sepsis both decrease eosinophil levels Asthma can cause a raised eosinophil cou nt, especially if there is associated eczema, but an absolute eosinophil count of >1 x 109/ L is very unusual and raises the possibility of an alternative diagnosis, such as Churg \200\223Strauss syndrome Normal eosinophil counts are below 0.4 x 109/L (1 \200\2233% of pe ripheral WCC) Counts of 0.4 x 109/L upwards can be seen in pulmonary eosinophilia. \200 \200 EOSINOPHILIC LUNG DISEASE 229 Table 25.1 Causes of CXR in \201 ltrates blood eosinophilia Condition Characteristic points Known asthma, with worsening symptoms, over weeks to months. Associated systemic symptoms. Raised blood eosinophil count, positive Aspergillus skin test, raised IgE, raised Aspergill us precipitins Asthma with allergic bronchopulmonary aspergillosis (ABPA) Foreign travel. Symptoms for days to weeks. Cough, malaise, anorexia, rhinitis, night sweat s, fever, dyspnoea, wheeze. Sputum contains eosinophils and larvae. Low- level blood eosino philia Simple pulmonary eosinophilia (L f \202 er \200\231s syndrome) Tropical pulmonary eosinophilia Foreign travel. Symptoms for weeks to months, with remissions and relapses. Cough, wheeze, sputum, dyspnoea, chest pain, fever, weight loss, fatigue. Sputum contains eosinophils. Rai sed blood eosinophil count, high IgE Chronic eosinophilic pneumonia Symptoms for weeks \200\223months, with associated systemic symptoms. Cough, sputum, haemop tysis, dyspnoea, recent onset asthma, fever, weight loss, night sweats. Sputum eosinophilia , but blood levels can be normal Acute eosinophilic pneumonia Short duration of symptoms, <5 days. Fever, cough, dyspnoea, and myalgia. Unwell, hypoxic. High BAL eosinophil count, no blood eosinophilia Hypereosinophilic syndrome Symptoms for weeks \200\223months. Associated systemic symptoms and other organ involvement . Fever, weight loss, cough, night sweats, pruritus. High blood eosinophil count Churg \200\223Strauss syndrome Rhinitis, past history of asthma. Other organ involvement. Associated systemic symptoms. Lo nger duration of symptoms, weeks \200\223months. Blood eosinophilia and eosinophilic tissue in \201 ltration Recent new drug. Possible associated skin reaction. Symptoms within hours \200\223days. Spe ctrum of illness, from mild to severely unwell, with cough, dyspnoea, fever, and hypoxia. E osinophilic tissue in \201 ltration, but blood eosinophilia not universal Drug-induced pulmonary eosinophilia 230 CHAPTER 25 Eosinophilic lung disease Causes of eosinophilic lung disease 1 Asthma and ABPA (see p 468) \200 Fever or worsening asthma symptoms may be caused by type 1 and 2 hypersensitivity reactions to Aspergillus fumigatus Untreated can cause central bronchiectasis CXR shows \202 eetin g shadows Blood eosinophilia Aspergillus skin prick test is positive and serum aspergillus IgG precipitins are positive. IgE levels are raised Treatment is with steroids and antifung al agents may be necessary. \200 \200 \200 Simple pulmonary eosinophilia (L f \202 er \200\231s syndrome) \200 Caused by parasitic infection, usually Ascaris lumbricoides, but also Strongyloides and Ank ylostoma Occurs worldwide, especially in SE Asia, Africa, Central and South America The egg s of the parasite are found in the soil and are ingested. After 10 \200\22314 days, larvae migrate from the intestine via lymph and blood to the liver and lung. From the lung, they p ass up the bronchial tree to be swallowed, to develop into roundworms in the gut The passag e of larvae through the lung causes an allergic reaction. This may be asymptomatic, but may cause cough, malaise, anorexia, rhinitis, night sweats, low-grade fever, occasional wheezi ng, and dyspnoea. The illness lasts around 2 weeks CXR shows transient bilateral shadows th at are discrete and perihilar. They disappear usually between 6 and 12 days, but can take u p to 1 month Sputum also contains eosinophils and larvae Blood eosinophilia at a low level Stool examination reveals parasites, but only 2 \200\2233 months later when the adult worms are passed Treatment is with an antihelminth agent, such as mebendazole for 3 days or leva misole as a single dose. Steroids may be necessary if the pulmonary manifestations are seve re. \200 \200 Tropical pulmonary eosinophilia \200 Hypersensitivity to migrating larvae of \201 larial worms Wucheria bancrofti and Brugia m alayi, similar to L f \202 er \200\231s syndrome Occurs in the Indian subcontinent, SE As ia, and the South Paci \201 c islands Insidious onset of cough, wheeze, sputum, dyspnoea, and chest pain, with associated fever, weight loss, and fatigue. Symptoms last for weeks to months, with remissions and relapses Examination reveals crepitations CXR shows bilateral uniform mottling of the lung \201 elds, especially in the middle and lower zones. There m ay be cavitation and pleural effusion Sputum and BAL contain eosinophils PFTs may be obstru ctive initially, but can become restrictive in longstanding untreated cases \200 \200 \200 CAUSES OF EOSINOPHILIC LUNG DISEASE 1 231 Histology shows eosinophilic bronchopneumonia and eosinophilic abscesses Blood eosinophil c ount is raised. IgE is raised Filarial complement test is positive Treatment is with a \201 laricide, diethylcarbamazine, for 3 weeks. This rapidly improves symptoms. \200 \200 Drug-induced pulmonary eosinophilia \200 Pulmonary shadowing develops within hours to days of starting the drug and resolves usually within 1 week of stopping it It is due to an allergic reaction in the pulmonary vessel wal l caused by the drug and occurs again on drug re-challenge There may be an associated skin reaction The drug should be avoided in the future and steroids given if necessary Severity of illness varies, from mild to severely unwell, with cough, dyspnoea, fever, hypoxia. May occur in those with concomitant asthma Tissue eosinophilia, but may not have blood eosinoph ilia Possible drugs include ampicillin, carbamazepine, chlorpropamide, cocaine (inhaled), d iclofenac, inorganic chemicals such as nickel, meth- otrexate, nitrofurantoin, penicillin, phenytoin, sodium aminosalicylate, sulphonamides, tetracycline. \200 \200 \200 232 CHAPTER 25 Eosinophilic lung disease Causes of eosinophilic lung disease 2 Chronic eosinophilic pneumonia \200 \200 \200 Unknown cause Women:men = 2:1. Occurs in middle age Insidious onset over weeks to months, w ith cough, sputum, possibly haemoptysis, dyspnoea, recent onset asthma, weight loss, night sweats, and high fever. Differential diagnosis includes TB Diagnosis is usually clinical an d radiological, but may need BAL or open lung biopsy CXR shows peripheral dense opacities w ith ill-de \201 ned margins (photographic negative of pulmonary oedema) CT shows periphera l air space in \201 ltrates Sputum eosinophilia BAL eosinophil count high Blood eosinophil ia may not occur. ESR is raised Treatment is with steroids, such as prednisolone 30 \200 \22340 mg/day, and improvement is usually rapid, with the CXR clearing within 2 \200\2233 d ays and normal in 2 weeks. Decrease steroid dose once stable, but continue for 6 months Rel apses common when steroids stopped and they may need further courses. \200 \200 \200 \200 Acute eosinophilic pneumonia Unknown cause, occurs in any age or sex. Presents with fever, cough, dyspnoea, and myalgia. Diagnostic criteria: Acute febrile illness of <5 days duration Hypoxic respiratory failure Interstitial or alveolar CXR in \201 ltrates BAL eosinophils >25% No parasitic, fungal, or other infection Prompt and complete response to steroids Failure to relapse after stopping steroids. \200 \200 \200 \200 \200 \200 May be unwell and hypoxic, requiring ventilatory support. No peripheral blood eosinophilia. High-dose steroids should be given until the respira- tory failure resolves and then the d ose can be tapered over 2 \200\2234 weeks. Hypereosinophilic syndrome \200 \200 \200 \200 Unknown cause. Rare Most common in men aged 30 \200\22340 Present with fever, weight loss, night sweats, cough, and pruritus Diagnosis based on: \200 \200 \200 Marked blood eosinophilia of >1.5 x 109/L for 6 months or more Signs and symptoms of eosino philic tissue in \201 ltration on histology No evidence of another cause of eosinophilia CAUSES OF EOSINOPHILIC LUNG DISEASE 2 233 Pulmonary involvement with interstitial in \201 ltrates and pleural effusions on CXR. Card iovascular involvement also occurs, with myocarditis, endocardial \201 brosis, restrictiv e cardiomyopathy, valvular damage, and mural thrombus formation. These may cause considerab le morbidity and mortality. Skin may be involved with urticaria and angioedema; CNS involve d with encephalopathy, arterial and venous embolism, peripheral neuropathy, or mononeuritis multiplex; GI tract with gastritis, nausea, diarrhea, alcohol intolerance and hepato- or s plenomegaly; joints with effusions and Raynaud \200\231s. Kidney and muscles can also be in \201 ltrated by eosinophils. Can be fatal Blood eosinophil levels may be as high as 70%. IgE levels are high Treatment is with high-dose steroids (e.g. 60 mg prednisolone), which i mproves about 50% of cases. May need to use other immunosuppres- sants, such as cyclophosph amide, hydroxyurea, azathioprine, or interferon alpha. Treatment should be tapered accordin g to falling eosinophil counts and end-organ improvement. \200 Churg \200\223Strauss syndrome (see p 660) \200 Severe asthma, blood eosinophilia, and pulmonary in \201 ltrates occur as part of a small and medium vessel vasculitis There may be eosinophilic tissue in \201 ltration ANCA usuall y, but not always positive Treatment with steroids and immunosuppression. \200 \200 This page intentionally left blank 235 Chapter 26 Extreme environments: \202 ying, altitude, diving Lung disease and \202 ying 236 Altitude sickness 238 Diving 240 236 CHAPTER 26 Extreme environments: \202 ying, altitude Lung disease and \202 ying Problems Flying presents problems for three reasons: \200 \200 \200 Extra hypoxia Volume changes in gas compartments Closed environment and disease transmissio n Extra hypoxia Some airplanes may be pressurized to the equivalent of about 5000 ft (1500 m) . This gives an atmospheric pressure of about 85 kPa and an FiO2 of about 18 kPa, compared with 21 kPa at sea level. In normal subjects this causes inconsequential falls in PaO2 and SaO2. However, some companies pressurize to the minimum allowed, 8000 ft (2400 m, same as some of the lower ski resorts in Colorado), FiO2 16 kPa (equivalent to breathing 15% O2 at sea lev el), and even in normal subjects the SaO2 may fall to 90% or so. The new Airbus 380 is pres surized to only 8000 ft, but the new Boeing 787, built from largely carbon \201 bre, will appar- ently allow greater pressurization and humidity levels. Patients with lung disease and a degree of hypoxia will be nearer the steep part of the hem oglobin dissociation curve, and will experience bigger proportional falls in oxygen carriag e by the blood. The estimated PaO2 at 8000 ft (the lowest cabin pressurization likely to be encountered) is estimated by the formula: Estimated PaO2 at 8000 ft = (0.24 x PaO2 at sea level) + (2.7 x FEV1/VC) + 3 e.g. sea level PaO2 = 8 kPa, FEV1/VC = 0.40, estimated PaO2 = 6 kPa. This is a rough approximation, and will vary considerably from patient to patient, particul arly due to differences in hypoxic drive. An alternative is to give the patient a hypoxic m ixture to breathe for 15 min minimum and measure the PaO2/SaO2. This is most easily achieve d by feeding a 40% Venturi mask with 100% nitrogen, which simulates a little under 8000 ft (equivalent to 16% O2). Even this will not necessarily predict that a patient will or will not run into trouble. Empirically, oxygen is often prescribed if the in- \202 ight PaO2 at 8000 ft, estimated from the above equation or by experimentation, is less than 7 kPa or 86 % SaO2. This is not evidence- based, so a simple recommendation based on sea level oximetry measure- ments is likely to be as valid. Simple recommendations for oxygen when \202 ying Sea level SaO2 SaO2 >92% SaO2 90 \200 \22392% SaO2 <90% No oxygen required Perform challenge test Recommend oxygen These are not quite the same as the BTS guidelines, which are more complex and consider com orbidities. 2 L/min via nasal cannulae, or 28% Venturi mask, is usually suf \201 cient to raise the SaO2 to sea level equiva- lent. Airlines vary as to whether they charge for this and at least a month should be allowed to arrange it. A MEDIF form or equivalent will requi re LUNG DISEASE AND FLYING 237 completion by the GP or specialist. Occasionally patients are allowed to bring their own ox ygen on board as hand luggage. Some airlines prohibit using oxygen during take-off and land ing. Volume changes in gas compartments Ascent to the equivalent of 5000 ft will increase g as in trapped compartments by 20%, and ascent to 8000 ft by nearly 40%. A pneumothorax or n on-communicating bullae will therefore increase by this amount. Therefore, it is advised th at patients with current pneumothoraces should not \202 y. In addition, it used to be adv ised not to \202 y within 6 weeks of a pneumothorax because of the slightly higher chance of a recurrence and the lack of adequate emergency medical treatment on board. This has re cently been changed to 1 week after full radiographic resolution or 2 weeks in the case of traumatic pneu- mothorax. The same arguments are applied to patients having had recent thor acic surgery (for whatever reason) who are now advised not to \202 y for 2 weeks after su rgery. None of this is really evidence-based and the risks of ignoring these guidelines are not known. It is probable that the risk of a second pneumothorax within this period is onl y high enough to worry about in patients with pre-existing lung disease. Closed environment Patients with infectious diseases such as TB should not \202 y. There seems to be a sign i \201 cant risk of infecting others. Further information Cottrell JJ Aircraft cabin pressures. Chest 1988; 98: 81 British Thoracic Society guidelines, www.brit-thoracic.org.uk/page246.html British Lung Foundation/BTS patient lea \202 et on \202 ying with a lung condition, www. brit-thoracic.org. uk/c2/uploads/air_20patient_20info.pdf BLF advice, www.britishlungfoundation.org/air-travel.asp 238 CHAPTER 26 Extreme environments: \202 ying, altitude Altitude sickness De \201 nitions of acute mountain or high altitude sickness are not prec ise, but include several symptoms provoked by the hypoxia. Pathophysiology Some of the path ophysiology is well understood and explains some of the symptoms and signs. These largely f all into two categories, minor and major. Minor, due to hyperventilation provoked by the hy poxia, and include: \200 \200 \200 \200 \200 \200 Light-headedness/fatigue Numbness/tingling of extremities Nausea/vomiting and anorexia Head ache Insomnia/sleep disturbance Periodic ventilation during sleep. These symptoms are common, develop over 6 \200\22312 h after arrival, and affect at least a fourth of those \202 ying to Colorado for a skiing holiday (altitude 2400 \200\2233400 m , 10 000 ft, barometric pressure 70 kPa, inspired oxygen tension 14.5 kPa, average SaO2 on arrival 89 \200\22390%). Most of the symptoms are due to a respiratory hypocapnic alkalosi s and resolve as the kidney \200\223], returning pH towards normal. This retains [H+] and excretes [HCO3 allows further hyperventilation and the rise in SaO2 helps resolve any of th e symptoms due to the hypoxia itself. This scenario tends to be common in those with a high er hypoxic drive (measured at sea level, as it encour- ages greater hypocapnia and alkalosi s). Confusingly, these symptoms may also indicate the early development of the more major c ategory. Major, those due to the hypoxia itself. These are more serious, can develop rapidly, and te nd to occur more in those with a lower hypoxic drive. There is also a genetic component in \202 uencing susceptibility, related to the ACE gene. In high altitude pulmonary oedema (H APE) the hypoxia provokes a non-uniform pulmonary vasoconstriction, raising pulmonary arter y pressure (PAP); hence some pulmonary capillaries are unprotected and receive the full ris e in PAP. Fluid leakage into alveoli, pulmonary oedema, and capil- lary damage (with pulmon ary hemorrhage) produce clinically apparent disease. The dominant symptoms/signs are: \200 \200 \200 \200 Extra breathlessness/cough Cyanosis Blood tinged frothy sputum Crackles on auscultation/rai sed JVP. In high altitude cerebral oedema (HACE) hypoxia also causes increased cerebral blood \202 ow, cerebral oedema, retinal hemorrhages, cerebral thrombosis, and petechial hemorrhages. The dominant symptoms are: \200 \200 \200 \200 Ataxia (may be the \201 rst sign) Confusion/disorientation/hallucinations/behavioral chan ge Severe headache/reduced conscious level Papilloedema. Both HAPE and HACE are potentially fatal. ALTITUDE SICKNESS 239 Management Risk factors are mainly the rate and degree of altitude attained. Keep ascent to \211 300 m/day and rest every third day. The minor form of altitude sickness is likely to resolve spontaneously over a few days with simple symptomatic treatment, analgesics, and p lenty of hydra- tion. However, prophylaxis, or early treatment on symptom appearance, with acetazolamide, is very effective, as are limiting further ascent and encouraging descent. A cetazolamide provokes a mild metabolic acidosis (by reducing [H+] availability for excretio n in the distal tubule) and \200\230pre- acclimatizes \200\231 the subject to allow greate r hyperventilation in response to hypoxia without the usual alkalosis. It is recommended wh en rapid ascent to altitudes \211 2500 m is unavoidable (such as a package ski trip to Asp en). 500 mg per day (slow release) for the 2 days prior to ascent is probably adequate for most subjects (or as treatment after symptoms develop). The commonest side-effect is a harm less and reversible tingling of the extremities. Temazepam has been shown to reduce the per iodic breathing at night (by reducing the arousals that help maintain the periodicity) and does not appear to worsen the hypoxia or reduce vigilance levels the following day. The best predictor of severe altitude sickness is a prior episode. It may be possible to pr edict likely problems based on sea level estimates of a poor hypoxic response, but this has not been fully validated. The management of the more severe forms of altitude sickness tha t tend to occur with rapid ascent to over 4000 m, pulmonary and cerebral oedema, is urgent. Management of severe altitude sickness \200 Increase inspired oxygen tension by rapid descent, extra inspired oxygen, or a local pressu rized environment (e.g. a portable hyperbaric chamber such as the Gamow bag) HAPE \200 \200 Sit upright and keep warm Nifedipine (20 mg bd up to qds + loading dose, 10 mg sublingually ) to reduce PAP Acetazolamide may help by also reducing PAP, as well as increasing the effe ctive ventilatory response to altitude hypoxia HACE \200 Dexamethasone (4 mg qds + loading dose, 8 mg) to reduce cerebral oedema. Improvement is usually rapid once the inspiratory oxygen tension is raised. Prophylaxis for this more severe form of altitude sickness is more contro- versial, but graded ascent is i mportant, acetazolamide probably helps, and nifedipine is used by some, particularly if the re is a history of a previous episode. Further information Information for patients. www.thebmc.co.uk/world/mm/mm1.htm Information for patients. www.familydoctor.org/247.xml Information for patients and doctors. www.high-altitude-medicine.com 240 CHAPTER 26 Extreme environments: \202 ying, altitude Diving Problems Increased recreational diving has raised the awareness of respiratory probl ems at depth. These can essentially be divided into \201 ve: \200 \200 \200 \200 \200 Barotrauma, e.g. ruptured bullae and pneumothorax Worsening of pre-existing disorder whilst at depth, e.g. asthma Nitrogen gas evolved from solution in body \202 uids Breath-hold d iving and ascent hypoxia Pulmonary oedema. Pathophysiology Barotrauma (second commonest cause of death in SCUBA divers after drowning) During descent, any air-containing cavity in the body will be compressed by the rise in ex ternal pressure. If there is any communication with the airways (e.g. middle ear, lung bull ae) then gas will slowly move into the air space. On ascent the airspace will expand and, i f air cannot escape quickly enough, may lead to rupture, of the eardrum or the bullae, for example. A tension pneumothorax can be rapidly fatal in this situation. Obstructive lung di seases in general can predispose to ruptured alveoli. In addition to pneumothoraces, the es caped air can produce a pneumome- diastinum, causing chest pain, and a radiolucent band (ai r in the pericar- dium) along the cardiac border on CXR. Breathing 100% O2 will clear the a ir more quickly. Air emboli can also occur and produce a wide range of symptoms; hyperbaric oxygen may be required. 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 