High altitude cerebral oedema This is a much more serious complication of hypoxia. Symptoms are headache, poor cerebral function, hallucina- tions, psychotic symptoms and ataxia. To the outside observer there is obvious poor decision making, the pres- ence of ataxia and co mmonly there are retinal haemor- rhages. The treatment is dexamethasone 8mg IV or IM then 4 mg 6-hourly and descent. High altitude pulmonary oedema This enigmatic condition is due to the leak of high protein oedema \202 uid into the alveoli with consequent loss of gas exchange. This condition is dif \201 cult to distinguish from pneumonia, heart failure and other pulmonary conditions CHAPTER 16.5 The effects of high altitude on the lung 407 AUTHOR \200\231S TIPS \200 \200 AUTHOR \200\231S TIPS \200 Altitude may worsen any respiratory illness. Patients with signi \201 cant lung disease sh ould seek med- ical advice prior to embarking upon travel to altitude. Acute mountain sickness is benign aslong as no further ascent occurs. Acetazolamide can be used as a pre- ventative agent. High altitude cerebral oedema results in confusion and atax ia. Treatment involves steroids and descent. High altitude pulmonary oedema results from lo ss of endothelial integrity and elevated pulmonary artery pressures. Requires treatment wit h descent, steroids and oxygen. Nifedipine may also help. Further reading Basnyat B, Gertsch JH, Johnson EW, et al. Ef \201 cacy of low-dose acetazo lamide (125 mg BID) for the prophylaxis of acute moun- tain sickness: a prospective, double -blind, randomized, placebo- controlled trial. High Alt Med Biol. 2003; 4(1):45 \200\22352. Burgess KR, Johnson P, Edwards N, et al. Acute mountain sickness is associated with sleep d esaturation at high altitude. Respirology 2004; 9(4): 485 \200\223489. Going to altitude with lung disease Asthma There have been very few studies on asthma but t here are potential bene \201 ts and draw-backs for the asthmatic going to altitude. The be ne \201 ts include the relative absence of allergens \200\223 particularly the house dust mite \200\223 at altitude; so, for the atopic asthmatic, altitude can often improve symp- toms and indeed was in the past used as a treatment for asthma. Opposing this bene \201 t of altitude is the relative hypoxia (hypoxic broncho-constriction) and, more impor- tantly , loss of humidity, leading to dehydration of the bron- chial mucosa. Finally, there is the known effect of cold air on bronchial muscle tone. Overall asthmatics do well at altitude but must remember to take their inhalers and a course of steroids with them in their backpa ck in case of emergency. Brutsaert TD. Genetic and environmental adaptation in high alti- tude natives. Conceptual, methodological, andstatistical concerns. Adv Exp Med Biol. 2001;502:133 \200\223151. British Thoracic Society. Managing passengers with respiratory disease planning air travel: British Thoracic Society recommenda- tions. Thorax. 2002;57(4):289 \200\223304. Grant S, MacLeod N, Kay JW, et al. Sea level and acute responses to hypoxia: do they predic t physiological responses and acute mountain sickness at altitude? Br J Sports Med. 2002;36 (2): 141 \200\223146. Hackett PH, Oelz O. The Lake Louise consensus on the de \201 nition and quanti \201 catio n of altitude illness. In: Sutton JR, Coates G, Houston CS (eds). Hypoxia and Mountain Medi cine. Burlington, Vermont: Queen City Printers, 1992: pp. 327 \200\22330. Imray CH, Myers SD, Pattinson KT, et al. Effect of exercise on cerebral perfusion in humans at high altitude. J Appl Physiol. 2005; 99(2):699-706. Epub 26 May 2005. COPD These patients are at particular risk on travel to altitude for a number of reasons. F irstly, they have a diminished gas exchanging surface and therefore the problem of diffusio n limitation is even greater. Secondly, they have \201 xed air \202 ow obstruction and t herefore the inability to raise ventilatory rates suf \201 ciently to cope with the hypoxi c environment. Thirdly, they are likely to already have alveolar hypoxia and pulmonary vaso constriction and this is potentiated by the environmental hypoxia. Kriemler S, Kohler M, Zehnder M, et al. High Alt Med Biol. 2006;7(3):256 \200\223261. Luks AM, Swenson ER. Travel to high altitude with pre-existing lung disease. Eur Respir J. 2007;29(4):770-792. Maggiorini M. High altitude-induced pulmonary oedema. Cardiovasc Res 2006;72(1):41 \200\22350. Peacock AJ, Jones PL. Gas exchange at extreme altitude: results from the British 40th Anniv ersary Everest Expedition. Eur Respir J 1997;10(7):1439 \200\2231444. Pollard, AJ, Murdoch, DR. The High Altitude Medicine Handbook. New York: Radcliff Medical Press 1997. Pulmonary vascular disease These patients are at particular risk at altitude and this was \201 rst shown in a case series of patients with pulmonary arterial atresia who developed high altitude pulmonary oedema when traveling to altitude. Because these patients already h ave pulmonary hypertension the addition of hypoxic pulmonary vasoconstriction to their cond ition can be fatal. With rare exceptions, patients with these groups of diseases are advise d not to travel to high altitude. Savourey G, Launay JC, Besnard Y, et al. Normo or hypobaric hypoxic tests: propositions for the determination of the individual susceptibility to altitude illnesses. Eur J Appl Physi ol. 2007; 100(2):193 \200\223205. Seccombe LM, Kelly PT, Wong CK, et al. Effect of simulated commercial \202 ight on oxygen ation in patients with interstitial lung disease and chronic obstructive pulmonary disease. Thorax 2004;59(11):966-970. Tsianos G, Eleftheriou KI, Hawe E, et al. Performance at altitude and angiotensin I-convert ing enzyme genotype. Eur J Appl Physiol. 2005;93(5-6):630 \200\223633. Sleep disorders As already stated earlier, normal people suffered from depressed ventilatio n during sleep with consequent alveo- lar hypoventilation and hypoxemia This is of course m ade worse at altitude so patients with sleep apnoea or hypop- noea are likely to do badly. Vachiery JL, McDonagh T, Moraine JJ, et al. Doppler assessment of hypoxic pulmonary vasocon striction and susceptibility to high altitude pulmonary oedema. Thorax 1995;50(1):22 \200 \22327. Weiss J, Haefeli WE, Gasse C, et al. Lack of evidence for association of high altitude pulm onary edema and polymorphisms of the NO pathway. High Alt Med Biol. 2003;4(3):355 \200\2233 66. Air travel in patients with lung disease It is not generally realized that the cabin altitu de of com- mercial aircraft is between 1830 \200\2232430m. This is not a prob- lem for norm al people but for people with lung disease the consequences of hypoxia can be severe. There are various sea level formulas for calculating likely arterial oxygen saturation levels in a commercial aircraft and these are quoted in the BTS and other guidelines. West JB, Schoene R, Milledge JS. High Altitude Medicine & Physiology 4th edn. London: Hodder Arnold 2007. Wu T, Kayser B. High altitude adaptation in Tibetans. High Alt Med Biol 2006:7(3); 193-208. D DENISON & M GLOVER 408 16.6 Diving Diving involves immersion in \202 uid, usually water but some- times other inhospitable m edia such as sewerage, or pres- sure exposure in a dry chamber. \200 not cause respiratory depression. Elevated PIO2, however, has been shown to reduce the vent ilatory response to exercise in some circumstances. Water, a non-breathable \202 uid with a higher density, vis- cosity, thermal capacity and conductivity than air, exposes the diver to pressures in excess of one atmosphere (approxi mately 100kPa) as, for every increase in depth of seawater of 10 meters, ambient pressure rises by approximately 100kPa. This can compromise inspiratory or expiratory effort, depend ing on the diver \200\231s attitude in the water, and neu- tralises gravitational pooling o f blood in veins of depend- ent limbs. Blood redistributes to the thorax, increases right h eart \201 lling and induces an immersion diuresis. Redistribution is potentiated by cold. Head-out immer- sion in water at 35 C (thermoneutral) reduces vital capacity by 5%, in 20 C by 10% and in 40 C by only 2%. Alveolar gasses at elevated pressure dissolve in greate r quantity in blood. The circulation delivers the gasses to other tissues into which they d iffuse and dissolve. Oxygen is consumed by the tissues and CO2 tension changes very little. Inert gasses, however, accumulate until each tissue is saturated and no more can be dissol ved at that pressure. The rate of saturation depends on a tissue \200\231s perfusion and it s capacity for dissolved gas. The \200\230slowest \200\231 tissues, those with the lowest ratio of perfusion to capacity, take more than 24 hours to saturate. The fastest take minut es. On ascent, ambient pressure falls and, with it, the amount of gas that can remain disso lved. Some of the excess inert gas remains in solution in the venous blood as it returns to the lungs but, after most dives, at least some is liberated as free gas. Venous gas emboli are usually trapped in the alveolar capillaries until resorbed and the excess gas is exhal ed. This lung \200\230 \201 lter \200\231 prevents gas emboli from reaching the sys- temi c circulation but it can be circumvented by right-left shunts such as patent foramen ovale or pulmonary arterio- venous malformation. These potential pathways for \200\230unde- serv ed \200\231 decompression illness can be identified using bubble-contrast echocardiography. Pulmonary oxygen toxicity PIO2 in excess of 50kPa causes a spreading tracheobron- chitis ty pically starting at the carina. Early symptoms are retrosternal tickle, accentuated by insp iration, and occa- sional cough. These become progressively more intense and widespread unt il constant burning exacerbated by inspiration, uncontrollable cough and, eventually, dyspn oea at rest occur. Earliest symptoms appear within 6 hours at a PIO2 of 79 \200\22389kPa, 4 hours at 101kPa and 1 hour at 303kPa. Chest signs can be absent but fever, atelectasis, th ick secre- tions, wheezes, crackles and bronchial breathing occur in advanced cases. Diffus e, bilateral opacities of varying extent are sometimes seen on CXR. Reduction in lung vol- umes and compliance, independent of any atelectatic effect of high fractional O2, have been demonstrated, as has reduced DLCO. Lower PIO2 of greater duration is associ- ated more wit h diffusion impairment while shorter expo- sure at high PIO2 preferentially affects lung me chanics. In general, alveolar-capillary permeability changes are thought to precede mechani cal changes, such as drop in vital capac- ity. The latter are usually detectable before sym ptoms are reported. Recovery after cessation of hyperoxia \200 Advanced changes can be irreversible, but symptoms typically diminish rapidly in 2 \200\223 4 hours with complete recovery in 1 \200\2233 days. An upper respiratory tract infection ca n cause symptom recurrence. Rates of onset and recovery tend to be symmetrical. Vital capac ity improves rapidly in the \201 rst few hours usu- ally returning to pre-exposure levels at around 30 \200\22335 hours, although some take several weeks. DLCO can correct almost c ompletely in hours but a small residual impairment can persist for over a week. Large chang es with rapid reversal are likely to be due to central nervous system oxygen toxicity, perh aps via a vagally mediated bronchoconstriction. \200 Carbon dioxide retention Gas density increases in proportion to ambient pressure. Work of b reathing, oxygen consumption, carbon dioxide production and physiological dead space increa se. Maximal voluntary ventilation falls. Hypoxia is unlikely at raised ambient pressure but CO2 removal may become critical when working hard at depth. Some individuals become hyperc apnic even when diving in favorable conditions. They often have a reduced ventila- tory res ponse to PICO2 or a high end-breath-hold PACO2 but these measurements are not suf \201 cie ntly speci \201 c or sensitive for prediction of this response which is also found in a sm aller proportion of non-divers. CO2 retainers can work hard underwater, enjoy good gas econ omy and avoid dyspnoea. They will, however, have lit- tle or no dyspnoeic warning of rising PICO2 in the event of equipment malfunction. Also, hypercapnia sensitizes to inert gas nar cosis, cerebral O2 toxicity, and decompression illness. Use of a less dense mixture, such a s oxygen- in-helium, reduces retention but the precise mechanism of the phenomenon remains unclear. Inert gas narcosis does Decompression illness Extravascular bubbles can occur in more severe decom- pression incide nts, but excessive intravascular bubbles probably cause the majority of cases of decompress ion ill- ness. Bubbles can embolise, damage vascular endothelium, induce \200\230foreign b ody \200\231 reactions or disrupt tissue, causing neurological, limb pain, cutaneous and ca rdiopulmonary manifestations. AUTHOR \200\231S TIP 90% of cases present within 6 hours of returning to the surface. If the venous bubbles overwhelm the capacity of the lungs to exchange gas, pulmonary capill ary endothelial damage, dyspnoea, hypoxia, and pulmonary oedema can develop. Some bubbles m ight pass to the left heart before they have been resorbed, causing embolic complications. A very heavy bubble load can cause haemodynamic compromise. First aid for decompression ill ness is basic life support, CHAPTER 16.6 Diving 409 oxygen and restoration of normovolaemia; de \201 nitive treat- ment is recompression. mean blood pressure and forearm vascular resistance, a greater increase in both when the he ad is cold challenged and an increased risk of developing hypertension. Immersion pulmonary oedema has occurred in warmer water especially during vigorous activity. Pulmonary capil- lary pressure is thought to be raised beyond plasma oncotic pressure by the combination of preload due to immersion with other factors such as increased cardiac output with, perhaps, overzealous rehydration, or greater afterload induced by the vascular reaction to cold. Pr essures across the alveolar-capillary wall can be exagger- ated further by breathing heavil y or against an inspiratory resistance such as narrowed airways or a faulty demand valve. T reatment is rest and oxygen. The oedema usually resolves within hours although diuretics ma y be used in more severe cases. In one survey of divers some 1.1% of respondents reported s ymptoms suggestive of pulmonary oedema. Some have recurrent episodes and should be advised against diving. Barotrauma and rupture \200 Barotrauma is mechanical damage due to compression or expansion of gas. Although thoracic b lood shift com- pensates for loss of gas volume and the lungs can toler- ate compression fa r beyond residual volume, extreme exposures will cause damage leading to oedema and haemopt ysis. If chest wall movement is unrestricted, lungs rupture when overpressurised by 9.3kPa, equivalent to ascent of barely 1m with closed glottis at total lung capacity or with a ful ly expanded, obstructed segment. If chest wall expansion is restricted 14.7kPa overpres- su re is required to cause rupture which is more likely to occur adjacent to less stiff areas of the chest wall. Gas can escape from the respiratory tract, including extrapulmonary site s, and present as pneumothorax, pneumomediastinum, subcutaneous emphysema, paren- chymal em physema or arterial gas embolism (AGE). AGE is a form of decompression illness which typica lly presents as diminution in level of consciousness or hemi- plegia/paresis during ascent or within 10 minutes of reaching surface. First aid is basic life support, oxygen and resto ration of normovolaemia; de \201 nitive treatment is recompression. Diving causes proporti onately fewer cases of pneumot- horax and more AGE than, for instance, intermittent positiv e-pressure ventilation or rapid decompression to altitude, perhaps because a diver \200\231 s chest wall is less compliant and splints the lung peripheries. Saltwater aspiration syndrome Anyone active in or around water is at risk of near-drowning or drowning, the \201 nal common pathway in most diving fatalities. Smaller amounts of as pirated seawater can cause cough, sputum, retrosternal discomfort and haemoptysis during or within 2 hours of a dive. Extrapulmonary features develop such as fever, aches, malaise an d even impaired consciousness. White cells can be elevated, PaO2 is often low and PaCO2 nor mal. Treatment is rest and oxygen. Warming often helps symptoms which usually resolve spont aneously within 6 to 24 hours. Respiratory disorder and \201 tness to dive In general a diver should have normal pulmona ry function. Any deficiency which compromises gas flow or gas exchange could predispose to injury or an inability to cope with the respiratory demands of diving. Contraindications to diving (BTS guidelines) \200 \200 \200 \200 Historical analyzes of submarine escape training show that 33% of victims had pulmonary bar otrauma (PBT) alone, 54% had neurological decompression alone and 13% had both. Only 5% of \200\230PBT alone \200\231 cases had signi \201 cant pneumothorax. \200 The true incidence of pneumomediastinum is not known as many are asymptomatic and only 50% are visible on a P-A CXR. Victims of PBT in submarine escape training are more likely to ha ve a low FVC. The reason for this is not fully understood but reduced compliance and lack o f support from the chest wall are two theories. No relationship has yet been demonstrated b etween PBT and FEV1/FVC. It must be noted, however, that candidates with obstruc- tive defe cts are screened out from submarine escape training. It is possible to rupture the respirat ory tract with force- ful exhalation against resistance or simply by maximal inhalation. Th is latter mechanism might be important in the rupture of lungs in divers who \200\230skip- breathe \200\231, deliber- ately holding themselves in prolonged inspiration in an attempt to reduce gas consumption. Asthma precipitated by exercise, cold, or emotion. Active tuberculosis. Pulmonary cystic \201 brosis. Lung bullae or cysts visible on chest x-ray \201 brotic lung disease. Active sarcoidosis. COPD. Uninvestigated pneumothorax. \200 \200 Speci \201 c questionable areas where diving permitted (BTS guidelines) \200 Asymptomatic asthma with normal spirometry, negative exercise test, PEF no more than 10% be low best values and requiring no more than regular inhaled anti- in \202 ammatory agents. In cured tuberculosis or resolved sarcoidosis with nor- mal chest radiography and pulmonary function testing. In spontaneous pneumothorax treated by bilateral surgi- cal pleurectomy, or healed traumatic pneumothorax, if associated with normal lung function and thoracic CT. Risk of recurrent spontaneous pneumothorax diminishes sharply if it does not recur in 2 ye ars. Professor Denison permits diving without pleurectomy if there is no recur- rence for 5 years and lungs are normal. In a review of 500 cases he noted that, if detailed lung funct ion is normal, CT adds little to plain CXR \201 ndings and concludes that the radiation d ose of CT cannot be justi \201 ed routinely for assessment of \201 tness to dive. Immersion pulmonary oedema Symptoms of dyspnoea can develop while immersed in cold water de spite minimal exertion, no aspiration of water, no evidence of cardiac dysfunction, no simi lar prob- lems previously and unimpaired exercise tolerance on land. Cough, sometimes produ ctive of blood and / or frothy spu- tum, and syncope are reported but no chest pain. Sympto ms typically resolve within hours but third heart sounds, basal crackles and X-ray changes consistent with pulmonary oedema might be found earlier. A history of immersion pulmonary o edema is associated with a higher D DENISON & M GLOVER 410 Long-term pulmonary effects of diving Findings vary. Some surveys show larger lung volumes, affecting vital capacity more than FEV1, attributed to respi- ratory muscle training from dense gas and equipment resistance. Reduced expiratory \202 ow rates at low lung vol- ume s have been found, possibly re \202 ecting small airway damage from bubble injury or chron ic oxygen toxicity, but with no obvious clinical consequences. Vital capacity in some diver sub-populations may decline at an accelerated rate. DLCO falls during saturation dives, wh ich last for many days but, once the dive is completed, it gradually returns to pre-dive va lues. Further reading British Thoracic Society guidelines on Respiratory Aspects of Fitness for Diving. Thorax 2003; 58: 3 \200\22313. Brubakk A, Neuman T (eds). Bennett and Elliott \200\231s Physiology and Medicine of Diving 5th edn. London: Saunders 2003. Edmonds C, Lowry C, Pennefather J, et al. (eds). Diving and Subaquatic Medicine 4th edn. London: Arnold 2002. Lundgren, CEG. Miller JN (eds). The Lung at Depth. New York: Dekker 1999. Wilmshurst PT, Nuri M, Crowther A, et al. Cold-induced pulmo- nary oedema in scuba divers a nd swimmers and subsequent development of hypertension. Lancet 1989; i: 62 \200\22365. This page intentionally left blank N JARAD 412 16.7 Occupational chronic obstructive pulmonary disease COPD is characterized by progressive fixed airflow obstruction. It is induced by inhaling n oxious material, ciga- rette smoke, being the best recognized and discussed else- where. A recent de \201 nition emphasized that the disease is in \202 ammatory and affects other s ystems as well as the lung. The two COPD \200\223 chronic bronchitis and emphysema \200 \223 have long been suspected to be induced by exposure to dust, organic material and fumes . The relationship between industrial exposure to dust and fumes and the develop- ment of o bstructive airway pattern has often been an area of controversy. Some of the reasons for th is are outlined in Table 16.7.1. (Figs. 16.7.1 and 16.7.2) and doubling the risk of chronic bronchitis and COPD even in the absence of any radio- logical changes of coal workers pneumonitis. The risk of COPD increas es with the duration and intensity of expo- sure and in exposure at a young age. The relati onship with emphysema in patients without pneumonitis is less clear. The relationship betwe en COPD and working on the sur- face of the mines or in open cast mines is less evident. A consensus has been that patients working on the surface handling loose coal are not associa ted with increased risk of chronic bronchitis. Table 16.7.1 Challenges in establishing relationship between occupation and COPD \200 \200 \200 Concomitant cigarette smoking Inconsistency of pattern of work in one occupation Exposure t o several materials in the same occupation Methods of diagnosis of chronic bronchitis and C OPD in epidemiological analyzes. Reliable comparative populations Estimation of exposure In dividual susceptibility \200 \200 A review of the literature on the relationship between chronic bronchitis and emphysema and occupational expo- sure was recently compiled by the Institute of Environmental Health a p art of the Medical Research Council (MRC). Predictably, concomitant cigarette smoking was o ne of the most signi \201 cant factors that have to be taken into account when regarding a material as independently responsible for causing chronic bronchitis and emphysema. An ind ependent relationship between an occupation and disease was regarded as present if there wa s doubling in the risk of chronic bronchitis and emphysema. Table 16.7.2 outlines occupatio ns associated with chronic bronchitis and emphysema independently from cigarette smoking. Fig. 16.7.1 Working in underground coal mines. The friable dust and the closed con \201 ne d environment are responsible for inhalation of respirable coal dust. Agricultural and farm workers Farmers and agricultural workers are exposed to hetero- geneo us groups of components including parts of animal manure, gasses that formed in silos and o rganic dusts. Farm workers were found to be at increased risk of decline in lung function t ests. The risk was more than doubled for those working with grains and in pig farms. Cotton textile workers The effect of cotton material on health is better recog- nised in th e form of occupational asthma (byssinosis). Cotton \201 bres, bacteria and endotoxines ar e all implicated in the bronchospasm induced by exposure to cotton. Reduced peak expiratory \202 ow rate, PEFR and FEV1 in sus- ceptible individuals is progressive. Airways disease becomes less reversible with continuous exposure The course of the disease and the symptom s resemble conventional COPD. People working with cotton textiles for more than one year ap pear to have a more than double risk of accelerated decline in lung function tests in the s hort and long term. Cessation of exposure is associated with cessation in lung function dec line. Table 16.7.2 Occupations associated with more than double risk of incidence of chronic bron chitis and emphysema Underground coal exposure Agricultural and farm workers Cotton textile workers Flour mill a nd bakery workers Welders \200 \200 \200 \200 Occupations associated with chronic bronchitis and COPD Coal dust exposure Due to political pressure, coal mining has been one occu- pation that attracted a signi \201 cant amount o f epidemiologi- cal and clinical research. There is an extensive body of literature that de monstrates a strong relationship between exposure to coal dust whilst working underground Flour mills and bakery workers Flour with its heterogeneous components is a well recog- nis ed sensitiser. As in cotton textile workers, repeated exposure especially in \202 our mil lers and bakers causes more than double risk of incidence of COPD especially in atopic indi viduals. Cessation of exposure is associated with CHAPTER 16.7 Occupational chronic obstructive pulmonary disease 413 Management: Cessation of exposure results in reduction of the decline in lung function in o ccupational COPD. In COPD associated with sensitisation, such as \202 our mill workers, b akers and cotton textile workers, lung function improvement was found after exposure was st opped. As there is an additive effect of cigarette smoking, suscepti- ble workers are urged to stop smoking. There is no evi- dence that screening for alpha-1 antitrypsin de \201 ci ency makes a signi \201 cant difference, mainly due to rare occur- rence of this condition . Management of symptoms and COPD exacerbation in patients with occupational causes is simi lar to COPD cases induced by cigarette smoking. cessation of decline in lung function and improvement of respiratory symptoms. Welders Welders are exposed to variety of particles, fumes and gasses (Fig. 17.7.3). Weldin g has a known association with occupational asthma and with COPD. Considerable evi- dence e xists of a relationship between welding and decline in lung function tests and the incidenc e of chronic bronchitis. The risk increases in current smokers. Further reading Chan-Yeung M, Enarson DA, Kennedy SM. The impact of grain dust on respiratory health. Am Rev Respir Dis 1992; 145:476 \200\223467. Enarson D, Chan Young M. Characterisation of health effects of wood dust exposure. Am Rev R espir Dis Am J Ind Med 1990; 17: 33 \200\22338. Glindmeyer HW, Lefante JJ, Jones RJ et al. Cotton dust and across shift change in FEV1 as p redictor of annual change in FEV1. Am J Respir Crit Care Med 1994; 149:584 \200\223590. Fig. 16.7.2 Workers in underground coal mine. Kibelstis A, Morgan EJ, Roger R, et al. Prevalence of bronchitis and respiratory obstructio n in American bituminous coal miners. Am Rev Respir Dis 1973; 168: 886 \200\223893. Rogan JM, Att \201 eld MD, Jacobson M et al. Role of dust in the working environment in de velopment of chronic bronchitis in British coal miners. Br J Ind Med 1973; 30: 217 \200\223 226. Rudd R. Coal miner \200\231s respiratory disease litigation. Thorax 1998; 53: 337 \200\223340. Rushton L. Review of literature on chronic bronchitis and emphy- sema and occupational expo sure. Publications of Institute for environment and health 2005. Sferlazza SJ, Beckett WS. The respiratory health of welders. Am Rev Respir Dis 1991; 143: 1134 \200\2231148. Fig. 16.7.3 A welder at work. A KHAN & N MASKELL 414 16.8 Asbestos-related diseases (excluding mesothelioma) Asbestos comprises of several naturally occurring \201 brous mineral silicates. Due to it s fantastic insulation qualities it was used extensively in the developed world until a 3 \200\2234 decades ago. Unfortunately, although the dangers of working with this material ar e well documented, it contin- ues to be used regularly in the developing world. BAPE BAPE tend to occur earlier following asbestos exposure than mesothelioma does. The ave rage latency is shorter than the development of pleural plaques. It is also an uncommon dia gnosis beyond 25 years after \201 rst exposure. This contrasts with malignant mesotheliom a with an expo- nentially rising incidence after initial exposure. The pleural \202 uid i s an exudate and may be blood stained but has no diagnostic characteristics. It is thought to be part of the in \202 ammatory pathway that occurs before the development of diffuse p leural thickening. Fiber types The serpentine fibers of chrysotile (white asbestos) are curly and \202 exibl e; these \201 bres penetrate less readily to the periphery of the lung than the needle li ke amphiboles. The most important amphilboles are: \200 \200 \200 crocidolite (blue asbestos); amosite (brown asbestos); and tremolite (a common contaminant of chrysotile). KEY POINT Benign asbestos pleural effusion is a diagnosis of exclusion Diffuse pleural thickening Diffuse pleural thickening of the pleura is less speci \201 c t o asbestos exposure than pleural plaque development. Thickening and \201 brosis of the vi sceral pleura occurs with fusion to the parietal pleura over a wide area. Diffuse pleural t hickening may result from exudative pleural effusions secondary to asbestos exposure, but o ther causes of pleural disease may also cause thickening (e.g. haemothorax, TB, chest surge ry, drugs such as methy- sergide and parapneumonic effusions). Diffuse pleural thickening o n a chest radiograph presents as a smooth non-interrupted pleural density extending for at least 25% of the lateral chest wall, with or without blunt- ing of the costophrenic angle. It has also been de \201 ned on CT scanning as a continuous sheet more than 5 cm wide, mor e than 8 cm in craniocaudal extent, and more than 3 mm thick. Diffuse pleural thickening ma y be dif \201 cult to dif- ferentiate from multiple pleural plaques, but the following may assist: \200 Range of asbestos related disease These include: \200 \200 \200 \200 \200 Asbestos pleural plaques. Benign asbestos pleural effusion (BAPE). Diffuse pleural thickeni ng. Asbestosis. Mesothelioma \200\223 pleura or peritoneum (covered in Chapter 14.7). Pleural plaques These can be calcified or non-calcified and affect the parietal pleura. The y tend to occur in areas of maxi- mum friction, i.e. the mid zones, diaphragms and pericar- dium. They tend to spare the costophrenic recess and apices. Pleural plaques take approxim ately 12 years to appear on chest radiographs and 20 years to calcify. They are dose relate d and plain chest radiology tends to underestimate their number and extent. These lesions d o not undergo malignant change. They do not cause disability or pain and can occur after li ght exposure. Fig. 16.8.1 shows a chest radiograph with bilateral calci \201 ed pleural pl aques plaques usually spare the costrophrenic angles and lung apices; diffuse pleural thickening due to asbestos exposure rarely calci \201 es; diffuse pleural thickening is ill-de \201 ned and irregular from all angles, whereas plaques are well de \201 ned; plaques rarely ex tend over more than 4 rib interspaces unless multiple and con \202 uent. CT is more sensitive and speci \201 c for the detection of dif- fuse pleural thickening th an chest radiography. Symptoms include breathlessness and chest pain and lung function test s show a restrictive ventilatory defect with reduced total lung capacity. A high resolution CT thorax is usually required as part of the initial work up (especially if pain is one of the symp- toms) In cases of diffuse pleural thickening the pleura will be smooth, with no involvement of the mediastinal border. Whereas, in mesothelioma the pleural is likely to be irregularly thickened with mediastinal involvement (See Fig. 16.8.2a, a diffuse pleural th ickening and 16.8.2b, mesothelioma). If there is diagnostic uncertainty a biopsy is recomme nded. Fig. 16.8.1 CXR showing bilateral calci \201 ed pleural plaques. CHAPTER 16.8 Asbestos-related diseases (excluding mesothelioma) 415 Patients with symptomatic diffuse pleural thickening may be eligible for compensation. KEY POINT Patients with pleural thickening involving the costo- phrenic angles are more lik ely to be symptomatic. Asbestosis Asbestosis is a diffuse interstitial \201 brosis of the lung caused by asbesto s dust. It tends to be prominent in the lower lobes and subpleural areas. Radiographically, other than the presence of pleural plaques there a re no unique characteristics to differe ntiate it from usual interstitial \201 brosis. Asbestosis seldom develops less than 20 ye ars after expo- sure and requires heavy asbestos exposure. Fig. 16.8.2a Chest CT scan showing diffuse pleural thickening. Pathogenesis \200 Incomplete phagocytosis of asbestos \201 bres results in release of lysosomal enzymes, fi brogenic factors, cytokines and free radicals \200\223 all leading to \201 brosis. Asbes tos bodies are usually seen within areas of \201 brosis. Clinical features \200 Presentation is usually with gradual exertional shortness of breath and a dry cough. Examin ation reveals late inspiratory \201 ne crackles. Finger clubbing occurs in 40% of patient s and is an adverse prognostic feature. Cyanosis and cor pulmonale may occur in advanced di sease. Investigations HRCT is more sensitive than plain radiography and should be performed in all suspected cases. (See Fig. 16.8.4.) \200 HRCT features include: Parenchymal bands. \200 Basal ground glass opacities. \200 Subpl eural curvilinear lines. \200 Interlobular septal thickening. \200 Fibrosis. \200 Asb estos bodies may be found in sputum, BAL is more sensitive in detecting asbestos bodies. Hi stological con \201 rmation of asbestosis is unnecessary unless there are atypical feature s. In these cases trans- bronchial biopsies are inadequate and a thoracoscopic or open lung biopsy will be needed. Fig. 16.8.2b Lobulated irregular pleural thickening in mesothelioma. Not uncommonly patients with diffuse pleural thickening may have an area of folded lung. Th is is also known as Blesovsky syndrome or rounded atelectasis. It develops as contracting v isceral pleura pulls and twists adjacent lung. This results is a subpleural opacity which o ften has a comet tail of vessels and bronchi converging toward the lesion (see Fig. 16.8.3) . Management No drugs are of proven value. In advance cases palliative measures such as oxyge n, diuretics, opioids should be used as appropriate. Prognosis and complications \200 Asbestosis usually progress slowly after removal from exposure and only 40% will progress o ver the following decade. There is an increased risk of lung cancer in patients with asbest osis. Due to the sensitivity of CT scanning some early cases are now being picked up in asy mptomatic individuals. More research is required into the natural history of this subgroup. Fig. 16.8.3 Early folded lung in a patient with diffuse pleural thickening. A KHAN & N MASKELL 416 Further reading ATS statement: Diagnosis and initial management of nonmalignant diseases re lated to asbestos. Am J Respir Crit Care Med 2004; 170: 691. Fletcher DE & JR Edge. 1970. The early radiological changes in pul- monary and pleural asbestosis. Clin Radiol 21:355-365 McLoud TC, BO Woods, CB Carrington, et al. 1978. Diffuse pleural thickening in an asbestos- exposed population. Am J Roentgenol 579-585 Lynch DA, G Gamsu& DR Aberle. 1989. Conventional and high resolution tomography in the diag nosis of asbestos-related diseases. Radiographic 9:523-551 Roggli VL, Oury TD, Sporn TA. Pathology of Asbestos-associated Diseases 2nd rev. edn. New York: Springer-Verlag 2004. Fig. 16.8.4 HRCT showing interstitial \201 brosis consistent with the diagnosis of asbest osis. 417 Chapter 17 Lung transplantation/ITU Chapter contents 17.1 Lung transplantation: considerations for referral and listing 418 17.2 Complications a fter lung transplantation 422 17.3 The care of lung transplant candidate or recipient 426 1 7.4 Acute respiratory distress syndrome 430 17.5 Severe acute respiratory syndrome 432 17.6 The ventilated patient 434 S PARKER & A FISHER 418 17.1 Lung transplantation: considerations for referral and listing Identifying potential lung transplant candidates Lung transplantation offers a realistic th erapeutic option to selected patients with end-stage respiratory disease who have failed to respond to maximal medical therapy. Poten- tial lung transplant recipients need to demonst rate under- standing of the risks and bene \201 ts of lung transplantation, appreciate the need for complicated mediation regimes and medication side-effects and be capable of and c ommit- ted to following speci \201 c guidance from healthcare profes- sionals within the t ransplant team. In the age of severe donor shortage it is essential that optimum use of thi s scarce resource occurs. This requires very careful assess- ment of potential candidates s o that only patients in whom the bene \201 t to risk ratio is favorable are taken on for l ung transplantation. Unstable psychiatric conditions: compliance with a com- plex medication regimen, regular at tendance at follow-up and early reporting of new symptoms are essential to pro- ducing good outcomes after lung transplantation. Patients who are unable to cope with these responsibi lities are at high risk of a poor outcome after transplantation. Relative contra-indications \200 Age >65 years for single and >60 for bilateral lung. \200 Poor rehabilitation potential. \200 Colonization with highly resistant micro-organi sms. \200 Obesity BMI >30. \200 Poor nutritional status BMI <18. \200 Severe symptoma tic osteoporosis. \200 Requirement for mechanical ventilation. \200 Critical or unstabl e clinical condition. \200 Other conditions causing signi \201 cant end-organ damage. Ad apted from International Guidelines for the selection of lung transplant candidates 2006 Up date. General guidance Indications and timing of referral Patients with end-stage lung disease who have failed to respond to maximal medical treatmen t can be considered for lung transplantation. Obviously many patients will have absolute or relative contra- indications and will not be suitable. Those in whom survival chance is es timated to be 50% at 2 \200\2233 years should be considered to have disease of suf \201 - cient severity for referral. Certain groups are at high risk of more rapidly progres- sive disease and are discussed below in disease speci \201 c guidance.