General aspects of hypersensitivity pneumonitis in Turkey

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pneumonitis in Turkey

Arif Hikmet ÇIMRIN¹, Özlem GÖKSEL², Yavuz Selim DEMİREL²

1Dokuz Eylül Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, İzmir,

2Ankara Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, Allerji Bilim Dalı, Ankara.

ÖZET

Türkiye’de hipersensitivite pnömonitisinin durumu

Türkiye’de bugüne kadar bildirilen hipersensitivite pnömonitisi prevalans oranları tetikleyici antijenlere maruz kaldığı bi- linen popülasyonda %5 ile 15 arasındadır. Türkiye’de hipersensitivite pnömonitisinin genel görünümünü sunmayı ve böy- lece gelişmekte olan ülkelerde göreceli olarak sık bir hastalığa ilgi çekmeyi amaçladık. Arama motorları ile Türkiye’den bil- dirilen olgular belirlendi. Elektronik veri tabanlarına kaydedilmeyen diğer dergi ve toplantı özetleri ise ayrıca incelendi. On üç yayından 22 olgunun demografik, klinik özellikler, çevresel ve mesleksel maruziyetler, tanısal yöntemler ve prognostik verileri çıkartıldı. Hastaların çoğu kadın (%68.2) ve kanatlı ile temas öyküsü pozitifti (%59). Ortalama maruziyet süresi 69

± 77.6 aydı. En sık olarak bidirilen klinik form kronik hipersensitivite pnömonitisiydi (%58.8). Temel patolojik bulgu reti- külonodüler paterndi (%45). Zorlu vital kapasite (FVC) restriktif bozukluk ve karbon monoksit difüzyon kapasitesinde azal- ma solunum fonksiyon testlerinde saptanan başlıca patolojilerdi. En sık patolojik bulgu insterstisyel fibrozisti (%61.5).Yet- miş milyon nüfustan bildirilen az sayıda kanatlılara maruziyetiyle kronik hipersensitivite pnömonitisi olması pek çok hi- persensitivite pnömonitisi olgusunun özellikle akut formların göz ardı edildiğini düşündürmektedir. Ayrıca, hipersensitivi- te pnömonitisi ihmal edilen bir meslek hastalığı olarak görünmektedir. Mevcut durum gelişmekte olan ülkelerde sık karşı- laşılan bir durum olarak kabul edilmeli ve mesleksel olarak risk altındaki gruplarda gecikmeden incelenmelidir.

Anahtar Kelimeler: Hipersensitivite pnömonitisi, kuş besleyenlerin akciğer hastalığı, mesleksel akciğer hastalıkları, Türkiye.

SUMMARY

General aspects of hypersensitivity pneumonitis in Turkey

Arif Hikmet ÇIMRIN¹, Özlem GÖKSEL², Yavuz Selim DEMİREL²

Yazışma Adresi (Address for Correspondence):

Dr. Özlem GÖKSEL, İzmir Atatürk Eğitim ve Araştırma Hastanesi, Allerjik Hastalıklar Ünitesi 35360 İZMİR - TURKEY

e-mail: [email protected]

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Hypersensitivity pneumonitis (HP) is a term most commonly used at present to describe a disease which was previously referred to as extrinsic allergic alveolitis. Although, called extrinsic allergic alveolitis in the past, it does not show any evidence of allergy such as skin test positi- vity, high IgE levels, and eosinophilia. It is an immune complex and cell-mediated immunologic disorder associated with production of specific precipitating antibodies directed against inhaled organic antigens (1). More than 200 different organic antigens consisting of plant products, ani- mal products, aerolized microorganism, and certain chemical compounds (e.g. isocyanates and zinc) can act as haptens which link to the host albumin to create an antigenic particle associated with the development of HP (1,2).

The incidence of HP is not exactly known at this time. A population-based study has estimated the annual incidence of interstitial lung diseases as 30/100.000 and HP accounted for less than 2% of these cases (3). Symptoms compatible with HP are seen in 9 to 12% of farmers and up to 15% of individuals who raise pigeons as a hobby. It has also been reported that up to 70%

of workers exposed to various antigens in mic-

robially contaminated office buildings develop HP (4-6). The prevalence of HP varies with environmental risk factors, including antigen con- centration, frequency and duration of exposure, antigen solubility, particle size, and use of respiratory protection in the work place. Moreover, individual susceptibility is one of the most important factors in the transformation of exposure to clinical diseases (1,2).

Occupational diseases including HP still keep their importance as a significant health problem in developing countries as these countries constitute 60% of universal labor force and 80% of this force work at small scale companies where heavy and dangerous duties are performed. Agricultural and industrial laborers working under unhealthy working conditions are under the threat of an increased risk of occupational diseases including HP (7,8).

Turkey has an important position among developing countries with a population of about 70 million. A study of the socioeconomic profile of Tur- key based on 2005 figures has revealed that 21.928.000 of 72.006.000 were employed. Even with an optimistic view taking into account 0.3- 0.5% occupational diseases incidence of Europe- an Union in 2002, over 20.000 new occupational

1Department of Chest Diseases, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.

2 Division of Allergy, Department of Chest Diseases, Faculty of Medicine, Ankara University, Ankara, Turkey.

Hypersensitivity pneumonitis prevalence rates are between 5 and 15% of the overall population exposed to known inciting antigens but a small number of cases have been reported from Turkey until now. We aimed to present a broad picture of hypersensitivity pneumonitis in Turkey, thus promoting interest in this relatively common disease in developing countries.

Search engines were utilized to retrieve the cases reported from Turkey. Other published journals and meeting abstracts which have not been registered into electronic databases were manually reviewed. Twenty-two cases from 13 reports we- re characterized by demographics, clinical features, occupational and environmental exposures, diagnostic tools and prog- nostic data. The majority of the group consisted of women (68.2%) and had a positive history for contact with an avian (59%). Mean exposure period was 69 ± 77.6 months. The most common reported clinical form was chronic hypersensitivity pneumonitis (58.8%). Reticulonodular pattern was the basic pathological finding (45%). Restrictive impairments of the for- ced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) of the lungs were the basic pathologies observed in pulmonary function tests. Interstitial fibrosis was the most common pathological finding (61.5%). Few cases reported with preponderance of chronic hypersensitivity pneumonitis with avian exposure from 70 million populations suggest that many hypersensitivity pneumonitis cases, especially acute forms, have been ignored. Also, hypersensitivity pneumonitis somehow appears to be a neglected occupational disease. The present situation should be considered as a common problem currently faced by developing countries and occupational groups under risk must be investigated promptly.

Key Words: Hypersensitivity pneumonitis, bird fanciers lung disease, occupational lung diseases, Turkey.

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diseases should be expected to be diagnosed in Turkey annually. Whereas, according to official statistics of Turkey, the incidence of all definitive occupational diseases including HP has been very low during the last 20 years (0.006%) (9-11).

Although HP can be expected to be a relatively common disease in these settings, only two work place-based cross sectional studies performed have failed to detect any HP cases from this country up to now (12,13). In our daily practice, we have also observed that there are small num- bers of HP cases published from Turkey in the literature. The limited number of HP cases reported and negative results obtained by screening studies have led us to study HP in detail. With this purpose, we have investigated the official national statistics and reviewed national and international literature comprehensively. Along with the cases we could reach, we aimed to ta- ke a broad picture of Turkey as a prototype of developing countries and to promote interest in HP in such countries.

MATERIALS and METHODS

Search engines were utilized to retrieve the cases reported from Turkey. “Hypersensitivity pneumonitis” or “extrinsic allergic alveolitis” were chosen as key words in PubMed search to investigate all studies, case reports and reviews ever published. Publications from Turkey were selec- ted among returned results. Another search was performed in Google and Turkish Medline where

“hipersensitivite pnömonisi” and “ekstrensek al- lerjik alveolit”, Turkish synonyms of “hypersen- sitivity pneumonitis” and “extrinsic allergic alveolitis”, were used as key words. Other published journals and meeting abstracts which have not been registered into electronic databases were manually reviewed. The HP cases were analyzed in detail according to their history, demographic patterns, occupational and environmental exposures, clinical features, laboratory and radiological findings, results of interventional diagnostic tools as well as treatment and prognostic data.

Recent guidelines regarding the diagnosis of HP were used to confirm if the patient fulfills four major and at least two minor criteria and if other diseases with similar findings have been exclu-

ded (1). The major criteria include: exposure to offending antigens revealed by history, by environmental measurements, or by the presence of antigen-specific IgG antibodies; symptoms compatible with HP appearing several hours after exposure; and abnormal chest radiograph. The mi- nor criteria include: basilar crepitant rales; decreased DLCO; decreased oxygen saturation; abnormal histology compatible with HP; and positive provocation test with offending antigen. We checked all cases if they were compatible with these criteria before including them in our study.

RESULTS

Two of the 13 reports presented 4 cases each one presented 3 cases, two presented 2 cases eachand the remaining 8 reports presented one case each (14-26). One case was presented both in a case series including 4 patients and also in a separate report (15,19). According to the diagnostic criteria, 1 of the 23 cases has been excluded from the study due to lack of evidence of HP. Therefore, 22 patients ranging in age from 5 to 62 years (mean age, 29.5 ± 16.7 SD) were evaluated. Demographic cha- racteristics, smoking, occupational and environmental exposure history of the 22 cases are presented in Table 1 and clinical findings and physical examination are presented in Table 2.

Presence of precipitating antibodies, arterial blood gases analyses, radiological findings and results of pulmonary function tests are shown in Table 3 while bronchoscopy (BAL and biopsy) findings, treatment and prognosis data are given in Table 4.

The majority of the group who consisted of women (n= 15, 68.2%) had a positive history of contact with avians (n= 13, 59%) of which pigeons accounted for 69.2%. Mean exposure period was 69 ± 77.6 months (Table 1).

The most common symptoms included cough, dyspnea, fever and malaise. Duration of symptoms ranged from one week to 20 years. The most common clinical form reported by various authors was chronic HP which was detected in 10 of the 17 cases (58.8%). Crackles were the most common physical finding present in 66.6%

of the patients (Table 2).

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Table 1. Demographic patterns and occupational & environmental exposures. ExposureDuration of References CasesAgeGenderOccupationSmokingtypeexposure 19*138MaleArchive clerkYesArchive dust5 months 144 cases22-264 HousewifeNot Indoor Not femalereportedmouldsreported 20117MaleSales clerkNoPigeon breeding4 months 21162FemaleFarmer NoHazel nut farmer20 years 22136MaleNot reportedNoPigeon breeding2 months 15 (4 cases)Case-1*This case was presented in reference 19. Case-245FemaleBird breederNoBird breeding3 months Case-336MaleArchive clerkNoArchive dust3 years Case-459FemaleBird breederNoBird breeding3 years 23142MaleBureaucrat Not Pigeon 15 years reportedbreeding 17Case-118MaleFarmerNoStraw mouldNot reported Case-219MaleFarmerYesStraw mouldNot reported 18Case-153FemaleHousewifeNoBudgerigar4 years breeding Case-244FemaleNot reportedNoBudgerigar5 years breeding 2415FemaleNoNoPigeon5 years breeding** 16 (family) Case-18FemaleNoNoPigeonMany breeding**years Case-2NotFemaleHousewifeNotPigeon Many reportedreportedbreeding**years Case-318↓FemaleNoNoPigeon Many breeding**years 25110FemaleNoNoPigeon 6 months breeding** 26114FemaleNoNoPigeon 2 months breeding** *This case was presented in a case series including 4 patients (11) and in a separate report also (15) because of its characteristic of treatment. **Indirectly exposure via another family member.

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Regarding the laboratory evaluation, precipitating antibodies were detected in 11 of the 13 cases giving a ratio of 84.6% (Table 3). There was lymphocytic alveolitis in BAL analysis of the majority of the cases (92.8%, 91.7% respecti- vely) and a decrease was observed in CD4/CD8 ratio (Table 4).

Reticulonodular pattern and ground glass pattern were the most common radiological findings observed in 20 cases assessed by means of chest radiography and 19 cases assessed by high resolution computerized tomography (HRCT) (n= 9 45%; and n= 6 31.6% respecti- vely). Chest radiography of one case was considered as normal. The most common reticulonodular patterns were micronodular pattern (n= 4, 20%) and ground glass pattern (n= 3, 15%) in chest X-rays, whereas ground glass pattern (n=

7, 36.8%), micronodular pattern (n= 5, 26.3%) and centrilobular densities (n= 4, 21%) were most frequent in HRCT (Table 3).

Restrictive impairments of the predicted forced vital capacity (FVC) and predicted carbon monoxide diffusing capacity of the lungs (DLCO) were the basic findings observed in pulmonary function tests. While FVC was found to be normal in 4 of the 18 cases (22.2%) where respiratory function testing was performed, FVC was reported to have decreased in the other 4 cases.

The mean FVC value of the 11 cases with results of pulmonary function tests was 59.4% of the expected value. DLCO decreased in 4 of the12 cases where DLCO was measured. The mean DLCO value was 67.6% of the expected figure for the 8 cases where detailed results were presented (Table 3).

Transbronchial biopsy (TBB) was performed in 13 cases and interstitial fibrosis was the most common pathological finding in 8 of the cases (61.5%). Results of the pathological examination of biopsy specimens were as follows: alveoli- Table 2. Clinical features.

Reference Cases Symptoms* Oscultation Duration of symptoms Clinical form

19 1 1, 2, 9, 12, 17 Crackles, ronchi 3 months Chronic

14 4 cases 1, 2, 3, 5, 6 Not reported Not reported Not reported

20 1 1, 2, 3, 5, 6, 7, 8, 9, 10, 11 Crackles 25 days Subacute

21 1 1, 2, 5 Crackles 20 years Chronic

22 1 1, 2, 3, 5, 12, 15 Crackles 2 months Not reported

15 Case-1 This case was presented in reference 19.

Case-2 1, 2 Crackles, ronchi 3 months Subacute

Case-3 2 Normal 3 years Chronic

Case-4 2 Normal 3 years Chronic

23 1 1, 2, 3, 6 1 year Subacute

17 Case-1 1, 2, 5, 12 Crackles 2 months Subacute

Case-2 1, 2, 5, 12, 13 Crackles 1 week Acute

18 Case-1 2, 5, 14 Crackles 2 months Chronic

Case-2 1, 2, 3, 7, 9, 15 Crackles 2 months Chronic

24 1 1, 2 Crackles 8 months Chronic

16 Case-1 1, 2, 5, 8, 10, 11, 16 Crackles 1 year Chronic

Case-2 1, 11, 16 Normal 1 year Chronic

Case-3 Asymptomatic Normal Not reported Chronic

25 1 1, 2, 5 Normal 3 months Acute

26 1 2, 3, 5, 6, 7 Crackles 1 month Acute

* 1. Dyspnea, 2. Cough, 3. Malesia, 4. Artralgia, 5. Fever, 6. Lost of weight, 7. Lack of appetite, 8. Hemoptysis, 9. Chest pain, 10. Palpitation, 11. Cyanosis, 12. Night sweating, 13. Head pain, 14. Back pain, 15. Sputum, 16. Clubbing, 17. Wheezing.

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Table 3. Laboratory and radiological findings. ReferenceCasesPrecipitin antibodyArterial hypoxemiaChest X-rays*HRCT*FVC%FEV1% FEV1/FVC% DLCO% 191NegativeNo 128788101 144PositiveNot1 in 2 cases NotDecreasedNotNotDecreased reported2 in 2 casesreportedin all casesreportedreportedin all cases 201Not doneYes 11, 23339100Not done 211PositiveYes1, 4Not done71717560 221Not doneYes 12596492Not done 151 Not done This case was presented in reference 19. 2Not doneYes 62, 5NNN55 3Not doneNo 55NNN44 4NegativeNo 11NNN64 231Not doneYes 1163??Not done 171Not doneYes5570738679 2Not doneYes55, 757699982 181Not doneNo88Not reportedNot reportedNot reported56 2Not doneNo55Not doneNot doneNot doneNot done 241PositiveNo2, 32, 3, 9Not doneNot doneNot doneNot done 161PositiveNoNot reported2, 94651100Not done 2 PositiveYesNot reported2, 9798398Not done 3 PositiveNo Normal3, 94953100Not done 251PositiveNo88, 5Not doneNot doneNot doneNot done 261PositiveYes 1Not done39Not doneNot doneNot done *1. Reticulonodular pattern, 2. Ground glass pattern, 3. Mozaik pattern, 4. Fibrotic changes, 5. Micronodular pattern, 6. Reticular pattern, 7. Diffuse consolidation, 8. Patchy infiltrations, 9. Centrilobular densities.

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Table 4. Results of interventional diagnostic tools, treatment and prognostic data. BALTreatment TransbronchialOpen lungCessation of ReferenceCasesLenfocyte (%)Neutrophil (%)Eosinophil (%)CD4/CD8biopsy*biopsy or VATS*exposureSteroids**Prognosis 19143.43.4Normal0.422, 52, 8No 2Good 144↑Not reportedNot reported↓4, 5Not doneYesNoGood 201N↑NormalNot done2, 5Not doneYes1Good 211672.46.20.28Not doneNot doneYes1Good 22143.2NormalNormal0.74Compatible with HPNot doneYes1Good 151This case was presented in reference 19. 2Not doneNot doneNot doneNot doneNot doneNot doneYes1Good 3↑NormalNormal0.05Non-diagnosticNot doneYesNoGood 4↑↑Normal40.53Non-diagnosticNot doneYesNoGood 231682Normal0.95Not doneYes1Good 17135Not reportedNot reported0.31Not doneYes1Good 2Not reportedNot reportedNot reported3.86Not doneNot doneYes1Good 18168.815.614.5Not doneNot done1Yes1Good 2501010Not done3, 5, 6Not doneYes1Good 241Not doneNot doneNot doneNot doneNot doneNot doneYes1Good 161Not doneNot doneNot doneNot doneNot doneNot doneYes1Good 2Not reportedNot reportedNot reportedNot reported7Not doneYes1Good 3Not doneNot doneNot doneNot doneNot doneNot doneYes1Good 251Not doneNot doneNot doneNot doneNot doneNot doneYesNoGood 261Not doneNot doneNot doneNot doneNot doneNot doneYes1Good *1. Non-necrotic granulomas, 2. Lymphocytic inflammation, 3. Interstitial inflammation, 4. Alveolitis, 5. Interstitial fibrosis, 6. Bronchiolitis, 7. Interstitial lung disease, 8. Non-specific chronic inflammation. **1. Systemic steroid, 2. Inhaled steroid.

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tis for 4 cases (30.8%), lymphocytic inflammation in 2 cases (15.4%) and interstitial inflammation, non-necrotic granuloma, bronchiolitis as well as interstitial lung disease ‘consistent with HP’ for each of the remaining cases (7.7%).

TBB did not yield any diagnostic value in 2 cases (15.4%). Open lung biopsy and video-assis- ted thoracoscopic surgery (VATS) were performed in two cases: one with TBB and one without TBB. Lymphocytic inflammation, non-specific chronic inflammation, and non-necrotic granuloma were the major findings (Table 4).

DISCUSSION

The starting point of the study was to draw attention to a limited number of HP cases in the literature from this country and to investigate the general features these cases. We have found a small number of published occupational HP cases including only 3 farmer’s lungs, 2 archives clerks’ HP and a few workplace screening studies with negative results (12,13,17,21). Although there is some focus on occupational causes of hypersensitivity pneumonitis, usually the most common causes are related to avian exposure in the home environment rather than work. The small number of cases may be related with mis- diagnosis of chronic forms or ignoring acute forms. Unpublished data and lack of standardiza- tion at our national system of reporting and re- gistering of health results seem to be the other major reasons. Nevertheless, it is obvious that HP appears to be as a neglected occupational disease in this country somehow. Occupational diseases still maintain their importance in developing countries and this situation should be considered as a common problem suffered by these countries. Screening of workplaces on a regular basis may be helpful to solve this problem.

Despite the limited number of cases, we have obtained some unexpected and interesting data from this series. Firstly, chronic HP was the most common form in this series. This form of disease is reported as the least common clinical presentation in the literature, whereas the acute form of HP that has a typical onset with influenza-like symptoms 4 to 8 hours after exposure to the inciting antigen is the most common clinical presen-

tation. A nationwide epidemiological survey from Japan conducted by Yoshizawa et al. surprisingly provided the chronic HP form to be more common similar to our results. The authors associated this result with smoking habits of the patients.

Smoking may reduce the acute immune response to antigens by suppressing antibody production and altering the cytokine profile secreted by macrophages, shifting the clinical picture to a rather chronic form (29). Unfortunately; cigarette smoking is still one of the most important health problems of Turkey, where approximately half of the population is active smokers (30). However, presence of only one active smoker in 10 cases of chronic HP (10%) does not support the theory that associates smoking with chronic form of HP.

The lower rate of acute forms may be related to underestimation of mild symptoms like flu by the patients at the beginning of exposure or poor diagnostic facilities in rural areas.

Secondly; the majority of the cases are females in our series as opposed to literature knowled- ge. Females constitute 68.2% of the presented cases. Raising parakeets or pigeons in houses, which is a common hobby among housewives in our country, may be responsible for this finding. Females are also employed in similar po- sitions as the male workers including agricultural activities in this country. Female hazelnut collectors with farmer’s lung diagnosis are an ideal example of this (21).

One important point indicated by this series is the fact that other family members also carry a high risk of HP although they do not raise the birds themselves (16,24-26). It should be noted that bird proteins have a high antigenic potenti- al and these antigens may be carried inside the house from the outer environment (i.e. balcony) via clothing of the bird raiser. Thus, screening of all the members of a bird raising family along with the index case for HP should not be neglected even though they may be asymptomatic.

Another important point indicated from these family cases is that antigens may persist in the environment even after the birds have been remo- ved. Thus, professional decontamination of all personal clothing and household should be un- dertaken after elimination of the birds (16).

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Pathogenesis of diseases is complicated and has not been revealed yet. Excessive immune response formed by humoral and cell-mediated mechanisms after exposure to inhaled organic antigens is the widely accepted concept for the basic responsible mechanism in the recent years.

However, development of HP in only a minority of exposed subjects placed the individual differen- ces in the first rank of responsible factors. HLA polymorphism has been associated with development of HP in a few genetic studies, but the genetic basis of the disease has not been fully elucida- ted (27). Yalcin et al. proposed that deficiency of selective IgA might lead to predisposition for bird antigens which can be easily carried in the patient’s respiratory units after their absorption. It is noteworthy that this concurrence has been decla- red for the first time in the literature (24).

Avoidance from responsible antigens before permanent radiological and physical damages develop is the most important step in HP treatment. In this series, 95.5% of the cases were reported to be kept away from the inciting antigens in the first line of the treatment. Avoidan- ce from antigens was sufficient for complete clinical improvement in 31.8% of the cases without any need for additional steroid treatment.

However, systemic steroid treatment was ne- eded for 63.6% of the cases while one patient was treated with inhaled steroid regimes. This chronic HP case which was treated successfully with long term high dose inhaled steroid admi- nistration may be the most interesting case from this series.

Systemic corticosteroids represent the only re- liable pharmacological treatment for HP but do not ultimately alter the long-term outcome. The use of inhaled steroids is anecdotal. Karnak et al. reported they preferred use of inhaled steroids as their patient had normal values of pulmonary function tests and DLCO, and a stable condition with mild symptoms. Inhaled flutica- sone propionate (2000 µg/day) was used for 16 months. Since the patient was reported as asymptomatic during the five-year follow-up period with normal findings in radiology, spiro- metric testing and arterial blood gas analyses, the authors recommended that high dose inha-

led steroids should be considered in the treatment of HP (19). Nevertheless, it should be kept in mind that this was only a case report and this observation needs to be supported by studies in large series.

A notable point about the treatment and prognosis is that all cases including chronic HP cases associated with pulmonary fibrosis have been successfully treated with conventional methods in contrast to the information in the literature.

An anticipated outcome would be better clinical response in the acute forms (1). This finding may be explained as a slowly progressive development of the disease as the patients were con- tinuously exposed to low concentrations of antigen and the cases were in the early stages of chronic disease without presence of end stage lung disease or cor pulmonale. Moreover, this series is a cross-sectional study of case reports collected from the literature and prognostic data only represent short term results of patients throughout the follow-up in the hospital.

Our research has some limitations. Firstly, only unusual or novel cases of hypersensitivity pneumonitis would be considered suitable for publi- cation in medical journals; therefore, assessing published case reports provides a very limited perspective on the prevalence or spectrum of the disease. We used published journals and meeting abstracts which have not been registered into electronic databases as well as data on Oc- cupational Lung Disease records by govern- ment; however, it would be necessary to review other sources of information such as Hospital Discharge Diagnostic Coding data.

In conclusion; this report predominantly inclu- des HP cases caused by prolonged exposure to domestic antigens (pet birds and indoor moulds). Although there is some focus on occupational causes of HP, the most common causes are often related to avian exposure in the home environment rather than work areas. Thus, pri- marily pet breeders and women seem to be under greater risk in houses. Few sporadic cases reported with preponderance of chronic forms have led us to think that many HP cases, especially acute forms of the disease, have been

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overlooked. Many of the chronic HP cases might be misdiagnosed as idiopathic pulmonary fibrosis. In fact, HP can easily progress into chronic forms if left untreated and early diagnosis is im- perative to prevent antigen exposure. Thus, screening of the occupational groups under risk may generate a significant public health effect by facilitating the diagnosis of a greater number of acute cases and reducing the number of chronic cases. We believe that this research will be a good first step to draw attention to the extent of HP in this part of the world.

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