Serial Plot 380 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 ) n M / L ( i F E P Mon 13/08/2001 Tue 14/08/2001 Wed 15/08/2001 Thu 16/08/2001 Fri 17/08/2001 Sat 18/08/2001 Sun 19/08/2001 Serial Plot 380 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 ) n M / L ( i F E P Mon 20/08/2001 Tue 21/08/2001 Wed 22/08/2001 Thu 23/08/2001 Fri 24/08/2001 Sat 25/08/2001 Sun 26/08/2001 Serial Plot 380 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 Sensitivity Speci \201 city Skin prick tests or speci \201 c IgE Variable <100% Often around 30% ) n M / L ( i F E P 3.2 x change in non-speci \201 c reactivity away from work ZPEF >44l/min pre/post shift Se rial PEF \211 4/day and \211 3 weeks 48% 64% 21% 77% Mon 27/08/2001 Tue 28/08/2001 Wed 29/08/2001 Thu 30/08/2001 Fri 31/08/2001 Sat 01/09/2001 Sun 02/09/2001 78% 92% Fig. 16.4.1 A 40-year-old smoking nurse presented with increasing asthma and time off work. She had had quite bad asthma from the age of 6 which had remitted in her teens. She was be tter on days away from work, and better when working night shifts when she would use less l atex gloves than on dayshifts. She was asked to keep 2-hourly measurements of peak \202 o w from waking to sleeping, a sequential plot of the record is shown here \201 gure. Shift s working at night are cross-hatched, periods sleeping are shaded. Her peak \202 ow drops over night shifts and over night when away from work. Serial PEF <4/day or <3 weeks 64% 83% Speci \201 c challenge test Unknown but <100% Unknown but <100% Sensitivity and speci \201 city of diagnostic tests for occupa- tional asthma Non-speci \201 c reactivity as measured with methacholine or histamine is not suf \201 ciently sensi tive on its own to exclude occupational asthma (sensitivity 70-95% in different studies). T he between visit variability in stable asthmatics has a 95% CI of around 3.2-fold. Changes greater than this after 2 weeks away from work have a sensitivity for the diagnosis of occu pational asthma of <50%. Testing is useful but not suf \201 ciently sensitive or speci \201 c on its own. Serial measurements of PEF are the most appropriate \201 rst step in t he physiological con \201 rmation of occupational asthma and should be started at the earl iest opportunity by the \201 rst clinician suspecting occupational asthma. The concept is simple but the precision is in the detail. Usual practice is to ask for approximately 2-ho urly reading from waking to bedtime, with treatment kept constant on work and rest days, an d times of starting and stopping work and waking and sleeping recorded each day. Suitable r ecord forms and instructions can be downloaded from http:// www.occupationalasthma.com/work ers.aspx. The interpretation of the recordings is much easier if plotted as Asthmatics have a diurnal variation in peak \202 ow which is usually lowest at the end of sleeping. As she works at night, the spontaneous diurnal variation might confound the reco rd. Fig. 16.4.3 shows the same data plotted as the mean value from waking, separately for n ightshifts and days away from work. The record shows similar waking values which increase a fter waking, but start to fall 8 hours after working on nightshifts. The bottom panel shows the time, the number of readings from which each datapoint is derived (blue days away from work, red work days, a minimum of 3 readings per datapoint required). The plot con \201 r ms that the night shift deterioration is not due to spontaneous diurnal variation. AUTHOR \200\231S TIP If you suspect occupational asthma start a 2-hourly record of PEF usin g published guidelines S BURGE 400 Average hour from waking for rest and night shift days 220 200 180 160 140 120 100 80 00 \200\22302 12 10 47 Total area between the graphs: 819 02 \200\22304 11 9 65 04 \200\22306 11 7 73 06 \200\22308 11 10 82 08 \200\22310 11 9 104 10 \200\22312 9 11 152 12 \200\22314 11 6 152 14 \200\22316 11 6 144 16 \200\22318 11 4 18 \200\22320 9 2 20 \200\22322 4 0 22 \200\22324 4 0 24 \200\22326 3 0 Hours from waking, number of readings and areas (night shifts) (rest) Fig. 16.4.3 Our nurse whose records are shown in Figs. 16.4.1 \200\22316.4.3 had speci \201 c challeng e tests as her ward used powder-free latex gloves which her employer thought had removed th e risk of latex allergy, also a domestic had developed occupa- tional asthma on the ward fr om a cleaning agent (benzalko- nium chloride) introduced to reduce the risks of cross infec tion. The results are shown in Fig. 16.4.4. The challenge clearly shows an immediate asthma tic reaction induced by donning and removing latex gloves, with no reaction follow- ing the use of nitrile gloves on another day. Her employer then knew what to remove from the work environment. Fig. 16.4.2 Shows the same data as Fig. 16.4.1 plotted as the daily maximum, mean and minim um by the oasys plotter. The upper panel shows the daily diurnal variation in peak \202 o w. The middle panel shows the predicted peak \202 ow (the black dotted line at the top of the record), an assessment of the likelihood of each complex showing occupational asthma ( 4 de \201 nitely yes to 1 de \201 nitely no); below this the daily maximum (blue dotted), mean (black bars) and minimum (red dotted) peak \202 ow. Nightshifts are cross-hatched, days away from work have a clear background. The bottom panel shows the date, the number of readings made per day and the number of hours worked. The deterioration on workdays in muc h more obvious on this plot. 2.20 2.10 2.00 1.90 Latex Blue nitrile 1.80 1.70 1.60 1.50 1.40 1.30 \210\2221 0 1 3 Hours from exposure 2 4 5 6 7 Speci \201 c inhalation tests are the gold standard for diagnos- ing occupational asthma, and are standard practice in some countries with good resources for occupational lung dis- ease (such as Finland, Belgium and Quebec). Occupational type bronchial provocation testing should not be attempted outside specialist centers. Control exposures with moni- toring fo r 24 hours after exposure should always be done \201 rst. Exposures to speci \201 c occu pational agents should start with exposures well below those at work and increase on subseq uent days if no reactions have occurred. Measuring non-speci \201 c reactivity before and after expo- sure may help in the interpretation of borderline reactions. The resources for occupational type provocation testing are very limited in the UK. In practice a patient com ing from a workplace with exposure to a well-identi \201 ed anti- gen and a positive PEF r ecord is suf \201 cient for clinical pur- poses; examples would include a laboratory rat h andler with a positive skin prick test to rat urinary antigen or a polyurethane molder from a workplace with isocyanate exposure where others have previously developed occu- pational asthma. Speci \201 c challenge tests are underused in the UK by international standards a nd are particularly valu- able when a worker is exposed to more than one possible cause, or the workplace has not had previous cases of occupational asthma. Fig. 16.4.4 Serial measurements of FEV1 after donning blue nitrile gloves on a control day and latex gloves on the next day showing an immediate asthmatic reaction with an equivocal late fall in FEV1 at 6 hours post exposure. Workplace challenges can be done when laboratory chal- lenges are impractical, for instance when the required heat is very high or the process too dangerous to reproduce in a hospita l laboratory. There are no externally validated standards for assessing a response, they sh ould not be attempted by non-experts. The principal is to establish a baseline for FEV1 or PEF away from exposure, usually with hourly measurements over some days, then to accompany your patient to their workplace to be exposed to the puta- tive agents while you monitor th eir response. You need to be able to cope with an acute asthmatic attack often in places wi thout healthcare resources. Many employers are unhappy about allowing access for this kind of test, which is little more than a supervised longitudinal recording of PEF. AUTHOR \200\231S TIP Never advise a patient with occupational asthma to leave their job unl ess you do not think they are \201 t to ever work again; advise their employer to remove them from exposure to the identi \201 ed cause. CHAPTER 16.4 Occupational asthma 401 Management after a con \201 rmed diagnosis The aims of management are \200 \201 rst exposure and \201 rst symptom (the shorter the better). I never advise the wor ker to leave their job, if you do your patient is likely to be unemployed, often for a long time (about one-third up to 6 years), and be poorer and less healthy because of poverty. N o action is likely to happen in the workplace to prevent further cases as the workplace has no requirement to notify a diagnosis of occupational asthma in past employees (at least in the UK). My advice to the worker is to be removed from the causative agent; this requires the cooperation of the employer who will need to know of the diagnosis. It is then up to th e employer to remove the cause or \201 nd suitable alternative employment. This is not al ways possible, in which case the worker will be dismissed or retired on medical grounds, al lowing immediate social support and sometimes an enhanced pension. Once the employer is tol d of the diagnosis, in the UK it is his responsibility to notify the disease under the RIDD OR scheme, which usually results in a visit from the factory inspectorate. Some workers are (rightly) concerned that communica- tion with their employer will result in their dismissa l. At least in the UK an employer has the right to dismiss a worker who is unable to do a p articular job, which may be the situation in a worker with occupational asthma. In this cas e I reiterate the advice in the letter that continuing exposure to the cause is likely to l ead to further loss of lung function and a worse prognosis in the long-term, and advise reg ular surveillance by myself or a clinician sharing care. Despite this general advice there are a minority of workers with occupational asthma who appear to tolerate further exposure without at least accelerated deteriora- tion in FEV1, however at present we have no method of identifying them at diagnosis. Improvement can continue for at least 2 years after remov al from exposure, and improvement in non-speci \201 c respon- siveness sometimes for longe r than this. Most agree than any assessment of residual disability should wait until remova l from exposure for 2 years. To remove the worker from the cause of their occupa- tional asthma. To maintain their worth while employment. To advise about compensation. To prevent others from developing occupatio nal asthma from the same workplace. To revise the risk assessment. (To preserve the viabili ty of the workplace from which your patient came). \200 \200 \200 The next steps depend on the social, occupational and political system under which you work . In many countries all workers have access to an occupational health service, in the UK th is is a minority. In theory the great majority of workers developing occupational asthma in the UK should have been under regular medical surveillance, following a risk assessment id entifying exposure to a respiratory sensi- tiser. In practice many are not, for instance he alth-care workers in workplaces using latex gloves should be under surveillance (MS25), but few are. When surveillance is car- ried out, it is frequently contracted to companies whos e contracts include only the questionnaires and lung function required for surveillance, ra ther than any responsibility for surveillance failures. In some countries (for instance, Ge rmany) the treating physician has the responsibility for completing the notification and co mpensation assess- ments; in the UK the employer has the responsibility for noti \201 cati on (under the RIDDOR regulations) while the worker has the responsibility for seeking compe nsation which is decided by non-medical adjudicators. For all action is required in the wor kplace which is outside the brief of most treating physicians. Unless the worker has been r eferred from the workplace to you, you require your patients consent to communicate with th e workplace, this is not always given. AUTHOR \200\231S TIPS \200 Prevention Occupational asthma is more likely when exposure levels are higher and when the asthmagen is more potent. Some substances can cause occupational asthma in more than 50% of exposed workers, examples include castor beans in animal feed mills and platinum salts in platinum re \201 ners. Catalytic car exhausts contain platinum, by substituting ammonium h exachlorplatinate with tetraamine platinum dichloride occupational asthma was prevented in those making the catalyst. In the health-care sector the substitu- tion of use of \200\230 powder-free \200\231 latex gloves has substantially reduced the incidence of latex allergy, which is further reduced by the substitution of latex with nitrile gloves allowing latex s ensitive workers to work in a latex-free (at least in the air) environment. The removal of glutaralde- hyde has prevented much asthma in endoscopy depart- ments, however biocides the mselves are a group of chemicals with sensitizing properties, perhaps by their abil- ity to denature protein. Biocides are responsible for at least some of the occupational asthma in cleaners and health care workers. Floors and surfaces are often sprayed with cleaning agen ts which contain potent biocides such as benzalkonium chloride and isothiozolinone. Obtain the consent of your patient before communica- tion with the employer or health and s afety executive Once you have con \201 rmed the diagnosis of occupa- tional asthma you sho uld inform your patient in writ- ing of the diagnosis. In the UK the \200\234date of knowl edge \200\235 has legal signi \201 cance as any common law claims should be made within th ree years of this date. The letter that I write is shown below. Dear I have told you today that in my opinion you have occu- pational asthma caused by \200 \200 \200 \200 \200 \200 \200 \200 You should no longer be exposed to this f or the best out- come for your asthma. If you continue exposure you are likely to have wors e asthma in the long term. You can claim for compensation from the Department of Works and Pensions using the forms I have given you. If you wish to make a common law claim you shoul d do this within three years of knowing the diagnosis. There is good evidence that early removal from exposure to the causative agent results in a greater chance of cure and less severe asthma in the remainder. Factors leading to a poor prognosis are the interval between the \201 rst work- related symptom and removal from ex posure, the severity of asthma at the time of diagnosis and the interval between Surveillance Workers exposed to respiratory sensitizing agents where there is a risk of occupational ast hma should be under S BURGE 402 regular surveillance, usually with a sensitive (but non-spe- ci \201 c) questionnaire and regular spirometry. This is the job of occupational health departments, but you may be aske d to see surveillance failures. Investigation with serial meas- urements of peak \202 ow is usually the \201 rst step in the con \201 r- mation or exclusion of occupational asth ma. Burge PS, Pantin CFA, Newton DT, et al; and the Midlands Thoracic Society Research Group, D evelopment of an expert system for the interpretation of serial peak expiratory \202 ow m easurements in the diagnosis of occupational asthma, Occup Environ Med. 1999; 56: 758 \200 \223764. Haz-Map, A Relational Database of Hazardous Chemicals and Occupational Diseases EditHaz-Map is an occupational toxi- cology database designed for physicians, physician assistants, occupational health nurses, and industrial hygienists to assist them in the recognition of diseases caused by toxic chemicals. Haz-Map links jobs to hazardous job tasks which are lin ked to occupational diseases and their symptoms. Further reading A comprehensive reference list on occupational asthma is available on www.o ccupationalasthma.com (under references). The evidence-based guidelines below are available in full on this website (Bohrf section). Help and forms for carrying out serial measuremen ts of peak \202 ow are in the workers section. http://hazmap.nlm.nih.gov Medical aspects of occupational asthma, MS25, HSE Books London: AsmaPro is an online occupational asthma database that can be searched by causative agent a nd job description. There is full and detailed information given on jobs, causative agents, substances, incidence, conditions, symptoms, methods of diagnosis, refer- ences and papers / abstracts. 1998. Nicholson PJ, Cullinan P, Newman Taylor AJ, et al. Evidence based guidelines for the preven tion, identi \201 cation, and management of occupational asthma, Occup Environ Med. 2005; 62: 290 \200\223299. http://www.remcomp.com/asmanet/asmapro/asma- work.htm Occupational asthma hazard prediction program: an online pro- gram to predict the occupatio nal asthma risk from any given chemical structure. This page contains links to the program and tools to help create the mol \201 les that the program uses. http://www.medicine.manchester.ac.uk/coeh/ research/asthma/ This page intentionally left blank C CHURCH & A PEACOCK 404 16.5 The effects of high altitude on the lung Introduction More than 140 million people on this planet live at alti- tudes of above 2500m and many others travel to high alti- tude on expeditions and on holiday. It is estimated, for example, that more than 30,000 Britons travel to Nepal where they will experience altit udes of up to 5500m (Everest base camp). The lung takes the brunt of high alti- tude exposu re. The lung is directly exposed to the external environment (just like the skin), but, unl ike the skin, its function can become severely compromised by the envi- ronmental assault p laced upon it. In this chapter I discuss the high altitude environment, discuss how this ef fects lung function (ventilation, gas exchange and the pulmonary cir- culation), describe t he particular syndromes peculiar to high altitude (acute mountain sickness, high altitude p ulmo- nary oedema and high altitude cerebral oedema), and con- sider how high altitude effe cts those with lung diseases wishing to travel to the higher regions of the planet or even to travel on a commercial aircraft. minus 70 C. The only available water is melted ice and the insensible loss of water due to respiration can be huge because all the inspired gas must be warmed and humidi- \201 ed to body values. It is recommended that climbers drink at least 3 litres a day at altitudes above 4000m. Cold: T falls by 6.5 per 1000m Hypobaric hypoxia: PiO2 falls by 13mmHg per 1000m \200 Dehydration: humidity falls, insen sible losses increase, water more difficult to obtain Fig. 16.5.1 Environmental changes in temperature, humidity and inspired PO2 at altitude. AUTHOR \200\231S TIPS \200 Effects of altitude include hypoxia, dehydration and cold. Climbers can loose large amounts of \202 uid through insensible mechanisms such as respiration. The high altitude environment The principle problem for humans traveling to high alti- tude is hypoxia. The fraction of oxygen in the air remains unchanged at 20.9% but, as we ascend , the atmospheric pressure falls and with it the partial pressure of oxygen. As a rule of t humb the atmospheric pressure is one-half of normal at 5500m, thus the partial pressure of oxygen is also one half of normal at that altitude. On the summit of Everest the atmospheri c pressure is only one-third normal and, until recently, it was thought to be impossible th at man could climb to that altitude without oxygen. In fact, Rheinhold Meissner and Peter H abeler did climb Everest without oxygen in 1978 and, since then, over 50 climbers have made it to the summit without the addition of bottled oxygen. These heroic physiological feats are rare however, and possible only for perfectly acclimatized supermen. The reason why som e people can cope with this extraordinary altitude and other cannot remains unclear, but it is likely to be due to individual physiological susceptibility as a conse- quence of genet ic adaptation. Not surprisingly, most peo- ple choose to live and work at lower altitudes, the highest place where people live continuously in North America is Leadville Colorado (30 94m). The highest place in the world where people live and work continuously is Chacaltaya, Bolivia at 5300m, but only one population has lived for thousands of years at high altitud e and that is the popula- tion living on the Tibetan plateau (approx. 3650m). The Tibetans have clearly adapted physiologically because the Tibetans, compared to lowlanders, maintain higher arterial oxygen saturation at rest and during exercise, and lose less aerobic perfo rmance with increasing altitude. This may be in part because they have larger lungs with be tter lung function and greater lung diffusion capacity than low- landers. Furthermore, they only develop minimal hypoxic pulmonary hypertension and have higher levels of exhaled nitr ic oxide than lowlanders or Andeans. The two other main environmental problems associated w ith high altitude are cold and dehydration (see Fig. 16.5.1). The fall in temperature is a feature of ascent; dehydration occurs partly because of the decreasing humidity of the air which falls to zero when the air temperature is below zero and also the decreased availabil ity of water. For example, on the summit of Mount Everest temperatures can fall to The effects of high altitude on the normal lung Ventilation Ventilation is controlled by th e hypercapnic response (HCVR) and the hypoxic response (HVR). At sea level our breathing is controlled by our PCO2 levels and PCO2 is held at about 5kPa. The hypercapnic response is linear. In contrast the hypoxic ventilatory response is S shaped to PaO2 (though linear to SaO2) and no real increase in venti- lation is seen until the inspired PO2 falls below 12kP a (approx. 3000m). At altitude, there is competition between the two control mechanisms bec ause, as hypoxia drives ventilation there is an increase in alveolar ventilation with fall in PaCO2, and hence PaCO2, which diminishes the hypercapnic response. Hypoxic ventilatory response and mountain performance Since gas exchange depends to a large extent on ventila- tion there have been many investigations into the hypoxic ventilatory r esponse of successful versus unsuccessful climbers and successful high altitude people vers us those that live at sea level. One of the greatest sociological experiments was the 1948 invasion of Tibet by lowland Chinese (Han people). Studies since that time have shown that the Han are much less able to cope with altitude than the native Tibetans. However, the Tib etans do not appear to have a brisker hypoxic ventilatory response. Likewise high altitude climbers do not necessarily have a better HVR than those who are less successful at altitud e, in particular Peter Habeler has a normal HVR and so do many successful 8000m climbers. V entilatory control is also important at night, during sleep. Naturally the oxygen saturatio ns fall slightly during sleep due to suppressed ventilation and it is thought that loss of ventilatory control leads to the charac- teristic Cheyne \200\223Stokes (periodic) type of breathing seen at altitude. (Fig. 16.5.2) It is likely that hypoxia during sleep is a signi \201 cant cause of altitude illness and prevention of this by the use of the carbonic anh ydrase inhibitor Acetazolamide may be a reason why people taking this drug are less suscept ible to acute mountain sickness. CHAPTER 16.5 The effects of high altitude on the lung 405 Parallel fall in SaO2 and PaO2 with increasing altitude 100 90 ) % ( 80 2 SaO2 O a S 70 r o ) g H m m 60 50 ( 2 O a P PaO2 Fig. 16.5.2 Mountaineer sleeping on oxygen at camp 3 (7600m) on Mt Everest. 9000 3000 4000 5000 6000 Altitude (m) 7000 8000 (a) Gas exchange Once the oxygen is into the lung then it must be exchanged for CO2 across the alveolar-capillary barrier. At sea level the gas exchange occurs one third the way along th e capil- lary and the amount of gas exchanged depends entirely on the pulmonary \202 ow r ate (perfusion limitation). At altitude because of the lower PO2 gradient across the alveol ar-cap- illary membrane and also because of the higher \202 ow rates due to higher cardia c output the exchange of gasses may be incomplete by the end of the capillary and there is relative hypoxemia due to the high venous admixture. This is called diffusion limitation an d is less severe in animals and man who have lived at high altitude for many generations. I nterestingly, gas exchange appears to better on the moun- tain than in simulated high altit ude chambers (see Fig. 16.5.3 (a and b) and Fig. 16.5.4). Experiments by both British and A merican teams have shown approximately a 1kPa (7.5mm Hg) difference in alveolar PO2 between cham- ber and \201 eld values at various altitudes up to and including the South Col of Everest (8000m). The American project (Operation Everest II) was performed using a hypobari c chamber in contrast to the actual ascent of Everest by the British team. The reasons for the better performance on the mountain than in a hypoxic chamber are unknown. Changes in PaO2 with altitude British Everest Expedition vs OEII 65 60 55 50 45 40 35 30 25 20 3530 4730 5288 5550 6460 6550 7467 7860 8000 8400 Altitude BEE 2 O a P AMREE OEII (b) Figs. 16.5.4a and 16.5.4b: Comparison of British Everest Expedition (BEE) results with Oper ation Everest II (OEII). Pulmonary circulation Unlike the systemic circulation the pulmonary vasculature constricts to hypoxia (hypoxic pulmonary vasoconstric- tion; HPV) This re \202 ex is present in all a nimals including man and birds so far studied. The purpose of HPV is two- fold: to keep the pulmonary circulation closed during ges- tation and also to promote matching of perfusion to ventilation when there is obstruction to ventilation such as inhaled foreign body or loc al lung disease. Unfortunately for normal people going to altitude this re \202 ex is mali gn because there is global hypoxia and hence pulmonary vasoconstriction leading to pulmonar y hypertension. The extent of hypoxic pulmonary vasoconstriction varies between individuals but, especially, between populations who are sea dwellers and populations who live at high alti- tude (e.g. Tibetans). It is highly likely that variation in the hypoxic pulmonary va soconstrictive response to hypoxia is an important feature of long term acclimatization to high altitude; for example the Yak, the Lhama and the Bar-headed Goose all have diminished hypoxic pulmonary vasoconstrictive responses yet function very well at altitude. (Fig. 16.5 .5) Fig. 16.5.3 Author measuring SaO2 in the Western Cym. C CHURCH & A PEACOCK 406 (Fig. 16.5.6) and indeed was thought to be due to these conditions until 1960 when the \201 rst formal description was made of a skier in Aspen and Colorado who suffered a sud- d en onset of breathlessness which responded very quickly to decent. High altitude pulmonary oedema is always pre- ceded by hypoxic pulmonary vasoconstriction with high pulmonary arter y pressures and it is likely that the aetiol- ogy is related to this pulmonary hypertension . Other important factors may be alveolar capillary damage and loss of endothelial integrit y. Symptoms are: breathlessness, orthopnoea, cough with haemoptysis, and chest discomfort. The principal sign is the presence of basal crackles. It is not surprising that the conditi on had previously been thought to be due to either chest infection or left heart failure. T he treatment is oxygen, dexamethasone and the oral calcium- channel blocker nifedipine with emergency descent. 39 Chacaltaya 32 ) g H m m Morococha ( La Paz 25 P A P Leadville n a e M Mexico City 18 Denver Lima Southampton 12 0 3500 9000 14500 20000 Altitude (feet) Fig. 16.5.5 AUTHOR \200\231S TIPS \200 At altitude ventilation is also controlled by hypoxia compared to control by PaCO2 at sea l evel Cheyne \200\223Stokes breathing occurs in sleep at altitude and can exacerbate hypoxia . This contributes to alti- tude related illness. Gas exchange at altitude can be diffusion limited. Hypoxic pulmonary vasoconstriction is a protective mechanism during gestation and in pulmonary disease in an attempt to maximize ventilation-perfusion match- ing. At altitu de it can result in global vasoconstriction and elevated pulmonary vascular pressures. \200 Diseases speci \201 cally related to altitude Acute mountain sickness Acute mountain sickn ess is a syndrome comprising head- ache, dizziness, dyspnoea, drowsiness, poor appetite and is often associated with nausea and poor sleep related to the Cheyne \200\223Stokes breath ing as described above. Acute mountain sickness is a relatively benign condition providing there is appropriate treatment and no further ascent occurs until the symptoms subside. If these warning signs are ignored it can go on to develop into full blown high altitude cereb ral oedema, with potentially fatal conse- quences. Severity of AMS is routinely assessed us ing the Lake Louise score. It can be prevented in many people by the use of the carbonic an hydrase inhibitor acetazolamide at a dose of 125 \200\223250mg BD. Acetazolamide is thought to work by acidifying the CSF and thus driving breathing. Fig. 16.5.6 CXR appearances of high altitude pulmonary oedema. Treatment of altitude illness Although there are bridging therapies that can be given to th ose who suffer the onset of altitude sickness, the most important treatment is descent. Ind eed, just a few hundred meters can make a major difference to a person \200\231s condi- ti on. It can be dif \201 cult on the mountain but it is critical if the subject is going to survive. Predicting those who are likely to get into trouble with altitude sickness There have been a great many studies looking at the vari- ous causative factors for high altitude illness a nd some of these studies are summarized in Further reading. On cur- rent evidence it would appear that: the hypoxic ventilatory response, lung \202 uid clearance and the hypoxic pu lmonary vasoconstrictor response are important elements that predispose the normal individu al to development of high altitude pulmonary oedema. Of these the hypoxic pulmo- nary vasoc onstrictor response is probably the most impor- tant and it is suppression of this by the c alcium-channel blocker and/or dexamethasone that is the most successful treatment. 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.