Brazilian Journal of Pulmonology

ISSN (on-line): 1806-3756 | ISSN (printed): 1806-3713


Publication continuous and bimonthly

SCImago Journal & Country Rank
Advanced Search


Current Issue: 2012 - Volume 38 - Number 3 (May/June)


Highlights of the Brazilian Thoracic Association Guidelines for Interstitial Lung Diseases

Destaques das Diretrizes de Doenças Pulmonares Intersticiais da Sociedade Brasileira de Pneumologia e Tisiologia


Bruno Guedes Baldi; Carlos Alberto de Castro Pereira; Adalberto Sperb Rubin; Alfredo Nicodemos da Cruz Santana; André Nathan Costa; Carlos Roberto Ribeiro Carvalho; Eduardo Algranti; Eduardo Mello de Capitani; Eduardo Pamplona Bethlem; Ester Nei Aparecida Martins Coletta; Jaquelina Sonoe Ota Arakaki; José Antônio Baddini Martinez; Jozélio Freire de Carvalho; Leila John Marques Steidle; Marcelo Jorge Jacó Rocha; Mariana Silva Lima; Maria Raquel Soares; Marlova Luzzi Caramori; Miguel Abidon Aidé; Rimarcs Gomes Ferreira; Ronaldo Adib Kairalla; Rudolf Krawczenko Feitoza de Oliveira; Sérgio Jezler; Sílvia Carla Sousa Rodrigues; Suzana Pinheiro Pimenta



Interstitial lung diseases (ILDs) are heterogeneous disorders, involving a large number of conditions, the approach to which continues to pose an enormous challenge for pulmonologists. The 2012 Brazilian Thoracic Association ILD Guidelines were established in order to provide Brazilian pulmonologists with an instrument that can facilitate the management of patients with ILDs, standardizing the criteria used for the diagnosis of different conditions and offering guidance on the best treatment in various situations. The objective of this article was to briefly describe the highlights of those guidelines.



As doenças pulmonares intersticiais (DPIs) são afecções heterogêneas, envolvendo um elevado número de condições, cuja abordagem ainda é um grande desafio para o pneumologista. As Diretrizes de DPIs da Sociedade Brasileira de Pneumologia e Tisiologia, publicadas em 2012, foram estabelecidas com o intuito de fornecer aos pneumologistas brasileiros um instrumento que possa facilitar a abordagem dos pacientes com DPIs, padronizando-se os critérios utilizados para a definição diagnóstica das diferentes condições, além de orientar sobre o melhor tratamento nas diferentes situações. Esse artigo teve como objetivo descrever resumidamente os principais destaques dessas diretrizes.



Keywords: Lung diseases, interstitial; Guidelines as topic; Brazil.


Palavras-chave: Doenças pulmonares intersticiais; Guias como assunto; Brasil.




Interstitial lung diseases (ILDs) are heterogeneous disorders, involving a large number of conditions, the approach to which continues to pose an enormous challenge for pulmonologists. In view of similarities in presentation, various forms of bronchiolitis are included in this group, as are alveolar filling disorders and pulmonary vasculitis.

The diagnosis of ILD is often delayed, largely because of a lack of knowledge on the part of health professionals and because of a lack of local resources. The prognosis and treatment of ILDs vary. In addition, no pharmacological treatment can change the course of certain ILDs. One of the major factors limiting the care provided to ILD patients in Brazil is the small number of health facilities with an appropriate multidisciplinary team, given that it is essential that expert pulmonologists, radiologists, and pathologists participate in the evaluation of patients with ILDs. In this context, the Brazilian Thoracic Association (BTA) Guidelines for ILDs were established in order to provide Brazilian pulmonologists with an instrument that can facilitate the management of patients with ILDs, standardizing the criteria used for the diagnosis of various pathologies and offering guidance on the best treatment in various situations. The objective of the present article was to briefly describe the highlights of the 2012 BTA Guidelines for ILDs.


One group of Brazilian experts with recognized experience in the treatment of ILDs was convened to develop ILD guidelines. An updated review of the major articles on ILD was carried out by searching the Medline, SciELO, and LILACS databases. An attempt was made to find the best available evidence, and the review was supported by the opinion of the expert panel. After all of the material was delivered, a final review was performed by all of the authors. The highlights of the 2012 BTA Guidelines for ILDs are herein divided into topics.

Classification of ILDs

A classification of ILDs was established in order to group the diseases by clinical, radiological, and histological criteria; to facilitate communication among health professionals; to facilitate the development of epidemiological registries and clinical trials; and, first and foremost, to improve patient management. Figure 1 shows the ILD classification, the highlights of which are as follows:

 the inclusion of smoking-related diseases, including smoking-associated fibrosis and combined pulmonary fibrosis and emphysema(1-3)
 the inclusion of bronchiolocentric interstitial pneumonia in the group of idiopathic interstitial pneumonias(4,5)
 the creation of a group of lymphoid diseases, characterized by lymphocyte proliferation(6)

Noninvasive diagnostic tests

In addition to detailed clinical examination and careful occupational history taking, emphasis was placed on noninvasive diagnostic tests, including chest X-ray, chest CT, pulmonary function tests, and exercise tests, the highlights of which are summarized below.

Patients with ILD can have normal chest X-rays. Therefore, the ILD guidelines emphasize the importance of examining chest X-rays for lung volumes, disease pattern, and disease distribution, as well as for extrapulmonary findings. In addition, it is essential that all previous X-rays be reviewed to determine whether the disease has progressed or become stable.(7) Chest HRCT, which should be performed during inhalation and exhalation, is described as playing a crucial role in the differential diagnosis of ILDs. In addition, when associated with the clinical and functional profile, chest HRCT findings can play a decisive role in the diagnosis of ILD. In patients with ILD, the most common HRCT patterns are the septal, reticular, cystic, nodular, ground-glass, and consolidation patterns.(8-10)

The guidelines describe the major functional changes observed in patients with ILD. The pattern that is classically associated with ILDs is a restrictive pattern, with decreased DLCO. Determination of DLCO is the most sensitive test, DLOC being often the first to be affected in ILD patients. Reductions in SpO2 can be observed at rest and during exercise.(11-13) Cardiopulmonary exercise testing and the six-minute walk test are the main methods for evaluating ILD patients during exercise. However, we should bear in mind that exercise limitation has a multifactorial origin, including ventilatory, cardiovascular, and peripheral factors. In ILD patients, the main objectives of functional evaluation at rest and during exercise include detecting airflow limitation in a timely manner and facilitating the differential diagnosis, as well as determining disease severity, treatment response, and prognosis.(12,13) Other tests can be performed on the basis of clinical suspicion.

Invasive diagnostic tests

The invasive diagnostic tests recommended in the ILD guidelines include BAL, transbronchial biopsy (TBB), and surgical biopsy. The guidelines emphasize that it is essential to correlate invasive test results with clinical and radiological findings, as well as with ancillary test results. Ideally, such correlations should be established by a multidisciplinary team including pulmonologists, radiologists, and pathologists.

The ILD guidelines emphasize certain aspects of BAL in the evaluation of ILD patients, including the appearance and cellular profile of the BAL fluid, as well as the presence of neoplastic cells, together with screening for infectious agents and cytopathic effects. A BAL is most important and most likely to aid in diagnosis in cases of diseases that present with ground-glass opacities, consolidations, and nodules on HRCT, such as sarcoidosis, hypersensitivity pneumonitis (HP), pulmonary alveolar proteinosis (PAP), alveolar hemorrhage, acute diffuse lung disease, eosinophilic lung disease, and infection.(14,15)

Regarding biopsies, the ILD guidelines emphasize that the decision of whether to perform TBB or surgical biopsy in ILD patients should take into account the clinical evaluation, including patient age, occupational history, and functional status, as well as the location and CT features of the lesions. The yield of TBB is higher than is that of BAL in cases of diseases that present with ground-glass opacities, consolidations, and nodules on HRCT, especially when there is bronchiolar and peribronchiolar involvement.(16,17)

Surgical biopsies can be performed by conventional limited thoracotomy (open lung biopsy) or by video-assisted thoracoscopy, with similar yields in ILD patients.(18) The choice of biopsy site should be guided by HRCT, and areas of honeycombing should be avoided.(19) Terminal lung, severe pulmonary dysfunction, (relative) pulmonary hypertension, and high cardiovascular risk are contraindications to the procedure.(20) Surgical biopsy should not be performed when there is a typical clinical and radiological profile, when the diagnosis is established by BAL or TBB, or when there is stable fibrosing disease with minimal repercussions.

Idiopathic pulmonary fibrosis

The diagnostic criteria for idiopathic pulmonary fibrosis (IPF), which are primarily based on recently published international guidelines, are presented, HRCT being given greater weight and surgical biopsy being dispensed with if the HRCT findings are characteristic of usual interstitial pneumonia (UIP). When biopsy is performed, it is recommended that a multidisciplinary team including pulmonologists, radiologists, and pathologists discuss the diagnostic approach.(21)

Various therapeutic studies were reviewed, and most showed disappointing results. No pharmacological treatment has proven effective in changing the course of IPF. Treatment is limited to palliative care, management of comorbidities, early referral for lung transplantation, and inclusion in randomized trials of new drugs. Although drugs such as pirfenidone, tyrosine kinase inhibitors, and N-acetylcysteine have been reported to have favorable prospects, results from ongoing studies are awaited.(21-24)

Nonspecific interstitial pneumonia

Regarding nonspecific interstitial pneumonia (NSIP), the guidelines emphasize the following(25-27):

 the two different forms of presentation of NSIP (i.e., fibrotic NSIP and cellular NSIP), according to the predominance of fibrosis or inflammation
 the need for thorough screening for underlying diseases, especially connective tissue diseases (CTDs), HP, and drug exposure
 a better response to corticosteroids and immunosuppressants when compared with that of UIP

Organizing pneumonia

In addition to a definition of organizing pneumonia (OP), the ILD guidelines present the major forms of OP, namely primary OP (cryptogenic OP) and secondary OP, and their most common causes, as well as the most important radiological patterns (i.e., consolidations, mass/nodule, and reticular opacities).(28-30) Furthermore, the guidelines describe the most commonly used diagnostic options and emphasize the favorable response to corticosteroids in most cases, despite the possibility of recurrence.(28,31)


The ILD guidelines describe the concept of sarcoidosis and recommend that etiologies for granulomatous tissue inflammation be ruled out. The guidelines also describe the diagnostic criteria for sarcoidosis; the disease is diagnosed on the basis of clinical, radiological, and histological findings, and tissue confirmation is not always necessary.(32)

The ILD guidelines emphasize that TBB is the primary method for diagnosing pulmonary sarcoidosis, transesophageal endoscopic ultrasound guided and endobronchial ultrasound guided fine-needle aspiration of lymph nodes being described as promising tests.(33,34) Ophthalmologic examination, cardiac evaluation, pulmonary function testing, chest X-ray, HRCT, blood workup, serum biochemistry, assessment of calcium metabolism, PPD testing, and urinalysis are recommended for all patients who have recently been diagnosed with sarcoidosis.

With regard to the treatment of sarcoidosis, the ILD guidelines state that spontaneous remission can occur, treatment being required in the following cases: presence of symptoms; significant systemic involvement (neurological involvement, myocardial involvement, or hypercalcemia); and pulmonary involvement with significant dysfunction or disease progression after a period of observation. In addition, the guidelines recommend that corticosteroids be used as the treatment of choice in most patients, the use of non-steroidal anti-inflammatory drugs, such as methotrexate (second-line treatment), azathioprine, leflunomide, TNF- antagonists, and antimalarials, being reserved for special cases, such as those in which treatment with non-steroidal anti-inflammatory drugs fails and those in which there are significant steroid related adverse effects.(32,35)


The most common exposures associated with HP are described in the ILD guidelines.(36) In addition, the diagnostic criteria for HP are defined, more weight being given to CT patterns suggestive of HP and to the possibility of confirming the diagnosis by BAL and TBB.(37) With regard to treatment, the guidelines emphasize the need for withdrawal from exposure; corticosteroids, which determine a better response mainly in the acute and subacute phases can be used.(37)


The ILD guidelines state that the CTDs that are most prevalent in ILD patients are progressive systemic sclerosis, polymyositis/dermatomyositis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and mixed connective tissue disease. The predominant patterns are NSIP and UIP; less common patterns include OP, bronchiolitis, and lymphocytic interstitial pneumonia.(38,39) The guidelines emphasize the need to be on the alert for extrapulmonary involvement, including respiratory muscle involvement and esophageal abnormalities, which can lead to pulmonary complications. In the initial routine evaluation and in the follow-up of CTD patients with pulmonary involvement, HRCT and full pulmonary function testing, with determination of DLCO, are recommended, as is assessment of respiratory muscle strength, in the presence of disease with possible muscle involvement.(40)

With regard to treatment, the possibility of periodic observation, without starting the patient on any medication, should always be considered, as should the possibility of referral for lung transplantation in advanced cases. When there is a need for treatment, initial options include a low-dose combination of cyclophosphamide and prednisone in cases of progressive systemic sclerosis and a corticosteroid with or without an immunosuppressant in cases of polymyositis/dermatomyositis.(41,42)

Smoking-related diseases

The major smoking-related ILDs are presented, including respiratory bronchiolitis with ILD, desquamative interstitial pneumonia, pulmonary Langerhans cell histiocytosis, IPF, combined pulmonary fibrosis and emphysema, and the recently described smoking-related pulmonary fibrosis, all of which can often be seen in the same patient.(1,3) Smoking-related ILDs have varied clinical, functional, radiological, and histological presentations, as well as having different prognoses. With regard to treatment, major emphasis is placed on smoking cessation, which can be sufficient to improve the patient's condition.(1,43)


The ILD guidelines describe the diagnostic criteria for lymphangioleiomyomatosis, with an emphasis on the fact that biopsy is not required in all cases.(44) In addition, the guidelines state that, in the presence of CT findings characteristic of lymphangioleiomyomatosis, serum VEGF-D levels constitute an important diagnostic criterion, although determination of VEGF-D levels is a test that is not widely available.(45) The guidelines also state that hormonal blockade (with progesterone or gonadotropin-releasing hormone analogues) can be used in severe or progressive cases (or both).(44,46) Furthermore, the guidelines present promising options for the treatment of lymphangioleiomyomatosis, including the use of doxycycline (a metalloproteinase inhibitor) and, mainly, the use of sirolimus (a mammalian target of rapamycin inhibitor). However, clinical trials are still needed in order to determine the actual role of these medications in the treatment of the disease.(47,48)


The ILD guidelines describe the major forms of PAP, namely autoimmune PAP (the most common form), secondary PAP, and genetic PAP, and emphasis is placed on the criteria for confirming the diagnosis of the disease, i.e., CT findings characteristic of PAP (crazy paving pattern), together with BAL and TBB findings, surgical biopsy being rarely required.(49,50) Regarding the therapeutic approach to PAP, the highlights are whole-lung lavage (current standard treatment) and, as a promising option, the use of subcutaneous or inhaled GM-CSF.(51-53)

Acute diffuse lung disease

The major causes of acute diffuse pulmonary infiltrates include infections, drug-induced pulmonary toxicity, acute interstitial pneumonia, acute interstitial pneumonia associated with CTDs, acute eosinophilic pneumonia, cryptogenic OP, HP, and diffuse alveolar hemorrhage.(54) For the evaluation of patients with acute diffuse pulmonary infiltrate, the most important ancillary tests are HRCT, bronchoscopy with BAL (with cytological and microbiological examination), TBB, and surgical biopsy.(55)

Acute exacerbation of ILD, classically associated with IPF, is defined by the following criteria: previous or concurrent diagnosis of IPF; unexplained development or worsening of dyspnea; HRCT showing a pattern consistent with UIP and new areas of ground-glass opacity, consolidation, or both; reduced oxygenation; and exclusion of infections and other diagnoses. Although the best treatment for acute exacerbation has yet to be defined, the guidelines recommend the use of moderate-dose corticosteroids or corticosteroid pulse therapy, either in isolation or in combination with cyclophosphamide.(56,57)

Pulmonary hypertension

The ILD guidelines emphasize that mathematical formulas can be used in order to predict the presence of ILD-associated pulmonary hypertension, given that echocardiography has significant limitations in identifying pulmonary hypertension in patients with ILD, producing a high number of false-positive and false-negative results. However, right heart catheterization remains the diagnostic method of choice.(58,59) In addition, the guidelines emphasize that there is currently no indication for the use of drugs that have an antiproliferative and vasodilating effect on the pulmonary circulation for the treatment of ILD-associated pulmonary hypertension.

Lung transplantation

The major indications for referral of ILD patients for an evaluation for lung transplantation are presented, as are the contraindications to the procedure. In addition, the guidelines emphasize the need for early referral of patients to lung transplantation centers, especially those patients with idiopathic interstitial pneumonia, given that transplantation is one of the few treatment modalities that have an impact on survival.(60,61)


1. Vassallo R, Ryu JH. Tobacco smoke-related diffuse lung diseases. Semin Respir Crit Care Med. 2008;29(6):643-50. PMid:19221962.

2. Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011;364(10):897 906. PMid:21388308 PMCid:3074462.

3. Katzenstein AL, Mukhopadhyay S, Zanardi C, Dexter E. Clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens. Hum Pathol. 2010;41(3):316 25. PMid:20004953.

4. de Carvalho ME, Kairalla RA, Capelozzi VL, Deheinzelin D, do Nascimento Saldiva PH, de Carvalho CR. Centrilobular fibrosis: a novel histological pattern of idiopathic interstitial pneumonia. Pathol Res Pract. 2002;198(9):577-83.

5. Yousem SA, Dacic S. Idiopathic bronchiolocentric interstitial pneumonia. Mod Pathol. 2002;15(11):1148 53. PMid:12429793.

6. Nicholson AG. Lymphocytic interstitial pneumonia and other lymphoproliferative disorders in the lung. Semin Respir Crit Care Med. 2001;22(4):409-22. PMid:16088689.

7. Raghu G, Brown KK. Interstitial lung disease: clinical evaluation and keys to an accurate diagnosis. Clin Chest Med. 2004;25(3):409-19. PMid:15331183.

8. Schaefer-Prokop C, Prokop M, Fleischmann D, Herold C. High-resolution CT of diffuse interstitial lung disease: key findings in common disorders. Eur Radiol. 2001;11(3):373-9. PMid:11288840.

9. Grenier P, Chevret S, Beigelman C, Brauner MW, Chastang C, Valeyre D. Chronic diffuse infiltrative lung disease: determination of the diagnostic value of clinical data, chest radiography, and CT and Bayesian analysis. Radiology. 1994;191(2):383-9. PMid:8153310.

10. Silva CI, Marchiori E, Souza Júnior AS, Müller NL; Comissão de Imagem da Sociedade Brasileira de Pneumologia e Tisiologia. Illustrated Brazilian consensus of terms and fundamental patterns in chest CT scans. J Bras Pneumol. 2010;36(1):99-123. PMid:20209314.

11. Chetta A, Marangio E, Olivieri D. Pulmonary function testing in interstitial lung diseases. Respiration. 2004;71(3):209-13. PMid:15133338.

12. Lama VN, Martinez FJ. Resting and exercise physiology in interstitial lung diseases. Clin Chest Med. 2004;25(3):435 53, v. PMid:15331185.

13. Alhamad EH, Lynch 3rd JP, Martinez FJ. Pulmonary function tests in interstitial lung disease: what role do they have? Clin Chest Med. 2001;22(4):715-50, ix.

14. Wells AU. The clinical utility of bronchoalveolar lavage in diffuse parenchymal lung disease. Eur Respir Rev. 2010;19(117):237-41. PMid:20956199.

15. Meyer KC, Raghu G. Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful? Eur Respir J. 2011;38(4):761-9. PMid:21540304.

16. Cazzato S, Zompatori M, Burzi M, Baruzzi G, Falcone F, Poletti V. Bronchoalveolar lavage and transbronchial lung biopsy in alveolar and/or ground-glass opacification. Monaldi Arch Chest Dis. 1999;54(2):115-9. PMid:10394823.

17. Leslie KO, Gruden JF, Parish JM, Scholand MB. Transbronchial biopsy interpretation in the patient with diffuse parenchymal lung disease. Arch Pathol Lab Med. 2007;131(3):407-23. PMid:17516743.

18. Miller JD, Urschel JD, Cox G, Olak J, Young JE, Kay JM, et al. A randomized, controlled trial comparing thoracoscopy and limited thoracotomy for lung biopsy in interstitial lung disease. Ann Thorac Surg. 2000;70(5):1647-50.

19. Sigurdsson MI, Isaksson HJ, Gudmundsson G, Gudbjartsson T. Diagnostic surgical lung biopsies for suspected interstitial lung diseases: a retrospective study. Ann Thorac Surg. 2009;88(1):227-32. PMid:19559230.

20. Lettieri CJ, Veerappan GR, Helman DL, Mulligan CR, Shorr AF. Outcomes and safety of surgical lung biopsy for interstitial lung disease. Chest. 2005; 127(5):1600-5. PMid:15888834.

21. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An Official ATS/ERJ/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med. 2011;183(6):788-824. PMid:21471066.

22. Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760-9.

23. Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079-87. PMid:21992121.

24. Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, et al; IFIGENIA Study Group. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005;353(21):2229-42. PMid:16306520.

25. Maher TM. Understanding nonspecific interstitial pneumonia: the need for a diagnostic gold standard. Am J Respir Crit Care Med. 2009;179(3):255-6; author reply 256. PMid:19158329.

26. Fischer A, West SG, Swigris JJ, Brown KK, du Bois RM. Connective tissue disease-associated interstitial lung disease: a call for clarification. Chest. 2010;138(2):251-6. PMid:20682528.

27. Corte TJ, Ellis R, Renzoni EA, Hansell DM, Nicholson AG, du Bois RM, et al. Use of intravenous cyclophosphamide in known or suspected, advanced non-specific interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis. 2009;26(2):132-8. PMid:20560293.

28. Cordier JF. Cryptogenic organising pneumonia. Eur Respir J. 2006;28(2):422-46. PMid:16880372.

29. Polverosi R, Maffesanti M, Dalpiaz G. Organizing pneumonia: typical and atypical HRCT patterns. Radiol Med. 2006;111(2):202-12. PMid:16671378.

30. Fortuna FP, Perin C, Bortoli J, Geyer GR, Porto NS, Rubin AS. O espectro clínico e radiológico da pneumonia em organização: análise retrospectiva de 38 casos. J Bras Pneumol. 2002;28(6):317-23.

31. Schlesinger C, Koss MN. The organizing pneumonias: a critical review of current concepts and treatment. Treat Respir Med. 2006;5(3):193-206. PMid:16696589.

32. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736-55. PMid:10430755.

33. Annema JT, Veseliç M, Rabe KF. Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis. Eur Respir J. 2005;25(3):405-9. PMid:15738281.

34. Garwood S, Judson MA, Silvestri G, Hoda R, Fraig M, Doelken P. Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis. Chest. 2007;132(4):1298-304. PMid:17890467.

35. Baughman RP, Costabel U, du Bois RM. Treatment of sarcoidosis. Clin Chest Med. 2008;29(3):533-48, ix-x. PMid:18539243.

36. Selman M, Chapela R, Raghu G. Hypersensitivity pneumonitis: clinical manifestations, pathogenesis, diagnosis, and therapeutic strategies. Semin Respir Med. 1993;14:353-64.

37. Lima MS, Coletta EN, Ferreira RG, Jasinowodolinski D, Arakaki JS, Rodrigues SC, et al. Subacute and chronic hypersensitivity pneumonitis: histopathological patterns and survival. Respir Med. 2009;103(4):508-15. PMid:19179061.

38. Antoniou KM, Margaritopoulos G, Economidou F, Siafakas NM. Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement. Eur Respir J. 2009;33(4):882-96. PMid:19336591.

39. Nicholson AG, Colby TV, Wells AU. Histopathological approach to patterns of interstitial pneumonia in patient with connective tissue disorders. Sarcoidosis Vasc Diffuse Lung Dis. 2002;19(1):10-7. PMid:12002379.

40. Wells AU. Pulmonary function tests in connective tissue disease. Semin Respir Crit Care Med. 2007;28(4):379-88. PMid:17764056.

41. Tashkin DP, Elashoff R, Clements PJ, Roth MD, Furst DE, Silver RM, et al. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med. 2007;176(10):1026-34. PMid:17717203 PMCid:2078679.

42. Labirua A, Lundberg IE. Interstitial lung disease and idiopathic inflammatory myopathies: progress and pitfalls. Curr Opin Rheumatol. 2010;22(6):633-8. PMid:20827201.

43. Patel RR, Ryu JH, Vassallo R. Cigarette smoking and diffuse lung disease. Drugs. 2008;68(11):1511-27. PMid:18627208.

44. Johnson SR, Cordier JF, Lazor R, Cottin V, Costabel U, Harari S, et al. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J. 2010;35(1):14-26. PMid:20044458.

45. Young LR, Vandyke R, Gulleman PM, Inoue Y, Brown KK, Schmidt LS, et al. Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases. Chest. 2010;138(3):674-81. PMid:20382711 PMCid:2940071.

46. Baldi BG, Medeiros Junior P, Pimenta SP, Lopes RI, Kairalla RA, Carvalho CR. Evolution of pulmonary function after treatment with goserelin in patients with lymphangioleiomyomatosis. J Bras Pneumol. 2011;37(3):375-9. PMid:21755194.

47. Pimenta SP, Baldi BG, Acencio MM, Kairalla RA, Carvalho CR. Doxycycline use in patients with lymphangioleiomyomatosis: safety and efficacy in metalloproteinase blockade. J Bras Pneumol. 2011;37(4):424-30. PMid:21881731.

48. McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011;364(17):1595-606. PMid:21410393 PMCid:3118601.

49. Borie R, Danel C, Debray MP, Taille C, Dombret MC, Aubier M, et al. Pulmonary alveolar proteinosis. Eur Respir Rev. 2011;20(120):98-107. PMid:21632797.

50. Huizar I, Kavuru MS. Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management. Curr Opin Pulm Med. 2009;15(5):491-8. PMid:19561506.

51. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med. 2002;166(2):215-35. PMid:12119235.

52. Venkateshiah SB, Yan TD, Bonfield TL, Thomassen MJ, Meziane M, Czich C, et al. An open-label trial of granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis. Chest. 2006;130(1):227-37. PMid:16840407.

53. Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, et al. Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 2010;181(12):1345-54. PMid:20167854 PMCid:2894410.

54. Tomiyama N, Müller NL, Johkoh T, Honda O, Mihara N, Kozuka T, et al. Acute parenchymal lung disease in immunocompetent patients: diagnostic accuracy of high resolution CT. AJR Am J Roentgenol. 2000;174(6):1745-50. PMid:10845517.

55. Bulpa PA, Dive AM, Mertens L, Delos MA, Jamart J, Evrard PA, et al. Combined bronchoalveolar lavage and transbronchial lung biopsy: safety and yield in ventilated patients. Eur Respir J. 2003;21(3):489-94. PMid:12662007.

56. Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr, et al. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176(7):636-43. PMid:17585107 PMCid:2094133.

57. Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37(2):356-63. PMid:20595144.

58. Zisman DA, Karlamangla AS, Kawut SM, Shlobin OA, Saggar R, Ross DJ, et al. Validation of a method to screen for pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Chest. 2008;133(3):640-5. PMid:18198245 PMCid:2655111.

59. Arcasoy SM, Christie JD, Ferrari VA, Sutton MS, Zisman DA, Blumenthal NP, et al. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. Am J Respir Crit Care Med. 2003;167(5):735-40. PMid:12480614.

60. Orens JB, Estenne M, Arcasoy S, Conte JV, Corris P, Egan JJ, et al. International guidelines for the selection of lung transplant candidates: 2006 update-a consensus report from the pulmonary scientific council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006;25(7):745-55. PMid:16818116.

61. Kreider M, Kotloff RM. Selection of candidates for lung transplantation. Proc Am Thorac Soc. 2009;6(1):20-7. PMid:19131527.

*Study carried out by the Interstitial Disease Committee, Brazilian Thoracic Association, Brasília, Brazil.
Correspondence to: Bruno Guedes Baldi. Avenida Dr. Enéas de Carvalho Aguiar, 44, 5º andar, CEP 05403-900, São Paulo, SP, Brasil.
Tel. 55 11 2661-5695. Fax: 55 11 2661-5695. E-mail:
Financial support: None.
Submitted: 4 May 2012. Accepted, after review: 11 June 2012.

About the authors

Bruno Guedes Baldi
Attending Physician, Department of Pulmonology, Heart Institute, University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil.

Carlos Alberto de Castro Pereira
Coordinator, Graduate Program in Interstitial Lung Diseases, Federal University of São Paulo/Paulista School of Medicine, São Paulo, Brazil.

Adalberto Sperb Rubin
Adjunct Professor of Pulmonology, Federal University of Health Sciences of Porto Alegre; Coordinator, Outpatient Clinic for Interstitial Diseases, Santa Casa Hospital Complex in Porto Alegre, Porto Alegre, Brazil.

Alfredo Nicodemos da Cruz Santana
Attending Physician and Supervisor of the Medical Residency Program, Department of Thoracic Diseases, North Wing Regional Hospital, State Department of Health, Brasília, Brazil.

André Nathan Costa
Collaborating Physician, Department of Pulmonology, Heart Institute, University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil.

Carlos Roberto Ribeiro Carvalho
Tenured Associate Professor and Director, Department of Pulmonology, Heart Institute, University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil.

Eduardo Algranti
Head, Department of Medicine, Fundação Jorge Duprat Figueiredo de Segurança e Medicina do Trabalho  -   FUNDACENTRO, Jorge Duprat Figueiredo Foundation for Occupational Safety and Medicine  - São Paulo, Brazil.

Eduardo Mello de Capitani
Associate Professor, Pulmonology Section, Department of Clinical Medicine, State University at Campinas School of Medical Sciences, Campinas, Brazil.

Eduardo Pamplona Bethlem
Associate Professor of Pulmonology, Universidade Federal do Estado do Rio de Janeiro  - UNIRIO, Federal University of the state of Rio de Janeiro  - Rio de Janeiro, Brazil.

Ester Nei Aparecida Martins Coletta
Adjunct Professor, Department of Pathology, Federal University of São Paulo/Paulista School of Medicine; Pathologist, Department of Anatomic Pathology, São Paulo Hospital for State Civil Servants, São Paulo, Brazil.

Jaquelina Sonoe Ota Arakaki
Attending Physician, Department of Pulmonology, Federal University of São Paulo/Paulista School of Medicine, São Paulo, Brazil.

José Antônio Baddini Martinez
Associate Professor, Department of Clinical Medicine; Coordinator, Department of Pulmonology, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, Brazil.

Jozélio Freire de Carvalho
Collaborating Professor, Department of Rheumatology, University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil.

Leila John Marques Steidle
Adjunct Professor, Department of Clinical Medicine, Federal University of Santa Catarina; Coordinator, Medical Residency Program in Pulmonology, Federal University of Santa Catarina University Hospital, Florianópolis, Brazil.

Marcelo Jorge Jacó Rocha
Physician in Charge of the Outpatient Clinic for Interstitial Diseases, Messejana Hospital, Fortaleza, Brazil.

Mariana Silva Lima
Physician in Charge of the Outpatient Clinic for Interstitial Diseases, São Paulo Hospital for State Civil Servants, São Paulo, Brazil.

Maria Raquel Soares
Pulmonologist, Outpatient Clinic for Interstitial Diseases, São Paulo Hospital for State Civil Servants, São Paulo, Brazil.

Marlova Luzzi Caramori
Collaborating Physician, Lung Transplant Group, Heart Institute, Federal University of São Paulo School of Medicine Hospital das Clínicas, São Paulo, Brazil.

Miguel Abidon Aidé
Associate Professor of Pulmonology, Fluminense Federal University, Niterói, Brazil.

Rimarcs Gomes Ferreira
Adjunct Professor, Department of Pathology, Federal University of São Paulo/Paulista School of Medicine, São Paulo, Brazil.

Ronaldo Adib Kairalla
Assistant Professor, Department of Pulmonology, University of São Paulo School of Medicine; Coordinator, Thoracic Center of Excellence, Hospital Sírio-Libanês, São Paulo, Brazil.

Rudolf Krawczenko Feitoza de Oliveira
Graduate Student, Department of Pulmonology, Federal University of São Paulo/Paulista School of Medicine, São Paulo, Brazil.

Sérgio Jezler
Pulmonologist, Federal University of Bahia, Salvador, Brazil.

Sílvia Carla Sousa Rodrigues
Attending Pulmonologist, São Paulo Hospital for State Civil Servants, São Paulo, Brazil.

Suzana Pinheiro Pimenta
Pulmonologist, Antônio Cândido Camargo Cancer Hospital, São Paulo, Brazil.



The Brazilian Journal of Pulmonology is indexed in:

Latindex Lilacs SciELO PubMed ISI Scopus Copernicus pmc


CNPq, Capes, Ministério da Educação, Ministério da Ciência e Tecnologia, Governo Federal, Brasil, País Rico é País sem Pobreza
Secretariat of the Brazilian Journal of Pulmonology
SCS Quadra 01, Bloco K, Salas 203/204 Ed. Denasa. CEP: 70.398-900 - Brasília - DF
Fone/fax: 0800 61 6218/ (55) (61) 3245 1030/ (55) (61) 3245 6218

Copyright 2019 - Brazilian Thoracic Association

Logo GN1