Airflow Obstruction in Sarcoidosis
1987; Elsevier BV; Volume: 92; Issue: 4 Linguagem: Inglês
10.1378/chest.92.4.582
ISSN1931-3543
AutoresMichael I. Lewis, David Horák,
Tópico(s)Sinusitis and nasal conditions
ResumoIn pulmonary sarcoidosis, much emphasis has been placed on the functional restrictive ventilatory defect evident in this condition. Little emphasis has been placed on airway dysfunction.In reviewing the pathology of sarcoidosis,1Carrington CB Gaensler GW Mikus JP Schachler AW Burke GW Goff AM Structure and function in sarcoidosis.Ann NY Acad Sci. 1976; 278: 265-283Crossref PubMed Scopus (140) Google Scholar it is not surprising that functional airway obstruction may be prevalent. Non-caseating granulomata occur in a perivascular, peribronchial distribution and may also be present in the bronchial mucosa. Bronchi in sarcoidosis may be affected by four different mechanisms2Berkmen YM Radiologic aspects of intrathoracic sarcoidosis.Sen Roentgenology. 1985; 20: 356-375Abstract Full Text PDF PubMed Scopus (22) Google Scholar; 1) airways may be narrowed by extrinsic compression by enlarged lymph nodes; 2) endobronchial sarcoidosis may occur in bronchi of any size, which may result in narrowing, occlusion, bronchial wall destruction and bronchiectasis; 3) fibrotic scarring of endobronchial lesions with resultant narrowing of bronchi may occur, as well as bronchial distortion by peribronchial, hilar or perihilar fibrosis; 4) extension of the granulomatous process into the bronchial wall from an extrabronchial location may ensue. It is of interest that severe bronchial stenoses of a number of segmental bronchi associated with severe airflow obstruction have been described in a patient with sarcoidosis, in whom resolution of the stenoses and improvement of physiologic function following the use of steroid therapy was reported.3Benatar SR Clark TJH Pulmonary function in a case of endobronchial sarcoidosis.Am Rev Respir Dis. 1974; 110: 490-496PubMed Google Scholar This study contrasts with that of Olsson et al4Olsson T Bjornstad-Pettersen H Stjernberg NL Bronchostenosis due to sarcoidosis. A cause of atelectasis and airway obstruction simulating pulmonary neoplasm and chronic obstructive pulmonary disease.Chest. 1979; 75: 663-666Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar who described six patients with single or multiple segmental bronchostenoses who presented with dyspnea and/or wheezing and in whom a poor response to steroid therapy was noted.A number of studies have evaluated airway function in patients with sarcoidosis.5Levinson RS Metzger LF Stanley NN Kelsen SG Altose MD Cherniack WS et al.Airway function in sarcoidosis.Am J Med. 1977; 62: 51-59Abstract Full Text PDF PubMed Scopus (68) Google Scholar, 6Argyropoulou PK Patakas DA Louridas GE Airway function in stage I and Stage II pulmonary sarcoidosis.Respiration. 1984; 46: 17-25Crossref PubMed Scopus (18) Google Scholar, 7Miller A Teirstern AS Jackler I Chuang M Sittzbach LE Airway function in chronic pulmonary sarcoidosis with fibrosis.Am Rev Respir Dis. 1974; 109: 179-189PubMed Google Scholar, 8Kaneko K Sharma OP Airway obstruction in pulmonary sarcoidosis.Bull Europ Physiopath Resp. 1977; 13: 231-240PubMed Google Scholar, 9Dines DE Stubbs SE McDougall JC Obstructive disease of the airways associated with stage I sarcoidosis.Mayo Clin Proc. 1978; 53: 788-791PubMed Google Scholar, 10Dutton RE Renzi PM Lopez-Majano V Renzi GD Airway function in sarcoidosis: smokers vs nonsmokers.Respiration. 1982; 43: 164-173Crossref PubMed Scopus (18) Google Scholar In a study by Levinson et al,5Levinson RS Metzger LF Stanley NN Kelsen SG Altose MD Cherniack WS et al.Airway function in sarcoidosis.Am J Med. 1977; 62: 51-59Abstract Full Text PDF PubMed Scopus (68) Google Scholar abnormal airway function was detected in 18 patients with sarcoidosis, all of whom had restrictive lung disease. In all patients, abnormal airway function was documented by at least one test and usually by multiple tests which included airway conductance, spirometry, frequency dependence of compliance, single breath nitrogen test, and assessment of upstream airway resistance. In a more recent study,6Argyropoulou PK Patakas DA Louridas GE Airway function in stage I and Stage II pulmonary sarcoidosis.Respiration. 1984; 46: 17-25Crossref PubMed Scopus (18) Google Scholar evidence of small airways dysfunction was evident in 39 nonsmoking patients with stage I sarcoidosis and 20 non-smokers with stage II sarcoidosis in whom abnormal test results suggestive of small airflow obstruction were noted in at least 30 percent of stage I patients (range 30-50 percent), and at least 44 percent of stage II patients (range 44-73 percent). Dines et al9Dines DE Stubbs SE McDougall JC Obstructive disease of the airways associated with stage I sarcoidosis.Mayo Clin Proc. 1978; 53: 788-791PubMed Google Scholar described five patients with stage I sarcoidosis associated with airways obstruction, four of whom presented with dyspnea, wheezing and cough. Analysis of flow volume relationships by Miller et al7Miller A Teirstern AS Jackler I Chuang M Sittzbach LE Airway function in chronic pulmonary sarcoidosis with fibrosis.Am Rev Respir Dis. 1974; 109: 179-189PubMed Google Scholar and spirometric measurements by Kaneko and Sharma8Kaneko K Sharma OP Airway obstruction in pulmonary sarcoidosis.Bull Europ Physiopath Resp. 1977; 13: 231-240PubMed Google Scholar indicated the presence of airways obstruction in 75 and 43 percent of patients, respectively, with various stages of sarcoidosis. Kaneko and Sharma8Kaneko K Sharma OP Airway obstruction in pulmonary sarcoidosis.Bull Europ Physiopath Resp. 1977; 13: 231-240PubMed Google Scholar suggested that in a proportion of their cases in whom a low peripheral airway conductance was noted, distorted peripheral airways may be responsible for the flow reduction documented. Dutton et al10Dutton RE Renzi PM Lopez-Majano V Renzi GD Airway function in sarcoidosis: smokers vs nonsmokers.Respiration. 1982; 43: 164-173Crossref PubMed Scopus (18) Google Scholar evaluated airway function in smokers and nonsmokers with sarcoidosis. They suggested that the combination of smoking and sarcoidosis was synergistic, resulting in small airways disease earlier in the course of the condition.Bechel and colleagues11Bechtel JJ Trammell S Dantzker DP Bower JS Airway hyperreactivity in patients with sarcoidosis.Am Rev Respir Dis. 1981; 124: 759-761PubMed Google Scholar evaluated nonspecific bronchial responsiveness to methacholine challenge in 20 patients with sarcoidosis, half of whom demonstrated increased airway reactivity. The responders tended to be more symptomatic with cough and wheeze and had a higher degree of baseline airways obstruction, as well as longer duration of disease. In a study by Presas et al12Presas FM Colomer PR Sanchon BR Bronchial hyperreactivity in fresh stage I sarcoidosis.Ann N Y Acad Sci. 1986; 465: 523-529Crossref PubMed Scopus (16) Google Scholar six of 12 patients with stage I sarcoidosis demonstrated enhanced responsiveness to methacholine. No differences in clinical symptoms or pulmonary function tests distinguished responders from nonresponders in this study. In contrast to the above two studies, Olafsson et al13Olafsson M Simonsson BC Hansson SB Bronchial reactivity in patients with recent pulmonary sarcoidosis.Thorax. 1985; 40: 51-53Crossref PubMed Scopus (24) Google Scholar found that stage I or II sarcoidosis seldom induces airway hyperreactivity in patients with normal spirometry, within one year of diagnosis.The occurrence of severe airflow obstruction in sarcoidosis has rarely been reported.14Zimmerman I Mann N Boeck’s sarcoid: A case of sarcoidosis complicated by pulmonary emphysema and cor pulmonale.Ann Intern Med. 1949; 31: 153-162Crossref PubMed Scopus (8) Google Scholar, 15Harden KA Barthakur A Cavitary lesions in sarcoidosis.Dis Chest. 1959; 35: 607-614Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 16Miller A The vanishing lung syndrome associated with pulmonary sarcoidosis.Br J Dis Chest. 1981; 75: 209-214Abstract Full Text PDF PubMed Scopus (17) Google Scholar In 1949, Zimmerman and Mann14Zimmerman I Mann N Boeck’s sarcoid: A case of sarcoidosis complicated by pulmonary emphysema and cor pulmonale.Ann Intern Med. 1949; 31: 153-162Crossref PubMed Scopus (8) Google Scholar described a 21-year-old black man with sarcoidosis characterized initially by hilar adenopathy and extensive bilateral infiltrates who progressed over ten years to develop severe airflow obstruction, emphysema and cor pulmonale. Autopsy revealed small bullae in various areas of the lung, as well as mild to moderate tubular bronchiectatic changes. Granulomata compatible with sarcoidosis were found in the lung and reticuloendothelial system. The alveolar air spaces varied in size and many were greatly distended with disruption of alveolar septa in some areas. Severe airflow limitation associated with giant bullous emphysema has been reported in three patients with sarcoidosis.15Harden KA Barthakur A Cavitary lesions in sarcoidosis.Dis Chest. 1959; 35: 607-614Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 16Miller A The vanishing lung syndrome associated with pulmonary sarcoidosis.Br J Dis Chest. 1981; 75: 209-214Abstract Full Text PDF PubMed Scopus (17) Google Scholar In two of these patients, resectional surgery (lobectomy) and bullectomies were performed with temporary improvement of symptoms. In both patients, enlarging bullae in the opposite lung were noted following surgery. In one patient, a second thoracotomy and bullectomy was performed16Miller A The vanishing lung syndrome associated with pulmonary sarcoidosis.Br J Dis Chest. 1981; 75: 209-214Abstract Full Text PDF PubMed Scopus (17) Google Scholar with significant palliation of symptoms for 18 months. We have recently reviewed a 65-year-old woman with longstanding sarcoidosis who presented with exertional dyspnea (Lewis MI, unpublished data). Chest radiograph and pulmonary function test results revealed significant hyperinflation and air flow limitation (FEV1 = 0.36 L; FEV1/FVC = 30 percent). She was a nonsmoker with normal levels of α1 antitrypsin who demonstrated progressive deterioration despite maintenance steroid therapy.In a long-term follow-up (minimum four years) of the course of airflow obstruction in patients with sarcoidosis and idiopathic pulmonary fibrosis, Meier-Sydow et al17Meier-Sydow J Rust MG Kappos A Kronenberger H Nerger K Schultze-Werninghaus G The long term course of airflow obstruction in obstructive variants of the fibrotic stage of sarcoidosis and of idiopathic pulmonary fibrosis.Ann N Y Acad Sci. 1986; 465: 515-522Crossref Scopus (2) Google Scholar found lack of progression of airflow obstruction in the majority of patients tested. It is clear, however, that a minority of cases with airway obstructive sarcoidosis may progress considerably, producing in some cases a condition not dissimilar physiologically from an “obliterative bronchiolitis type syndrome.”18Epler GR Colby TV The spectrum of bronchiolitis obliterans.Chest. 1983; 83: 161-162Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar Whether early administration of corticosteroids may prevent or attenuate airway obstructive sarcoidosis is not known. The studies of Benatar and Clark3Benatar SR Clark TJH Pulmonary function in a case of endobronchial sarcoidosis.Am Rev Respir Dis. 1974; 110: 490-496PubMed Google Scholar and Smellie et al19Smellie H Apthorp GH Marshall R The effect of corticosteroid treatment on pulmonary function in sarcoidosis.Thorax. 1961; 16: 87-91Crossref Google Scholar suggest that improvement in pulmonary function is possible. This contrasts with the experience of Olsson et al4Olsson T Bjornstad-Pettersen H Stjernberg NL Bronchostenosis due to sarcoidosis. A cause of atelectasis and airway obstruction simulating pulmonary neoplasm and chronic obstructive pulmonary disease.Chest. 1979; 75: 663-666Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar as well as our own. In pulmonary sarcoidosis, much emphasis has been placed on the functional restrictive ventilatory defect evident in this condition. Little emphasis has been placed on airway dysfunction. In reviewing the pathology of sarcoidosis,1Carrington CB Gaensler GW Mikus JP Schachler AW Burke GW Goff AM Structure and function in sarcoidosis.Ann NY Acad Sci. 1976; 278: 265-283Crossref PubMed Scopus (140) Google Scholar it is not surprising that functional airway obstruction may be prevalent. Non-caseating granulomata occur in a perivascular, peribronchial distribution and may also be present in the bronchial mucosa. Bronchi in sarcoidosis may be affected by four different mechanisms2Berkmen YM Radiologic aspects of intrathoracic sarcoidosis.Sen Roentgenology. 1985; 20: 356-375Abstract Full Text PDF PubMed Scopus (22) Google Scholar; 1) airways may be narrowed by extrinsic compression by enlarged lymph nodes; 2) endobronchial sarcoidosis may occur in bronchi of any size, which may result in narrowing, occlusion, bronchial wall destruction and bronchiectasis; 3) fibrotic scarring of endobronchial lesions with resultant narrowing of bronchi may occur, as well as bronchial distortion by peribronchial, hilar or perihilar fibrosis; 4) extension of the granulomatous process into the bronchial wall from an extrabronchial location may ensue. It is of interest that severe bronchial stenoses of a number of segmental bronchi associated with severe airflow obstruction have been described in a patient with sarcoidosis, in whom resolution of the stenoses and improvement of physiologic function following the use of steroid therapy was reported.3Benatar SR Clark TJH Pulmonary function in a case of endobronchial sarcoidosis.Am Rev Respir Dis. 1974; 110: 490-496PubMed Google Scholar This study contrasts with that of Olsson et al4Olsson T Bjornstad-Pettersen H Stjernberg NL Bronchostenosis due to sarcoidosis. A cause of atelectasis and airway obstruction simulating pulmonary neoplasm and chronic obstructive pulmonary disease.Chest. 1979; 75: 663-666Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar who described six patients with single or multiple segmental bronchostenoses who presented with dyspnea and/or wheezing and in whom a poor response to steroid therapy was noted. A number of studies have evaluated airway function in patients with sarcoidosis.5Levinson RS Metzger LF Stanley NN Kelsen SG Altose MD Cherniack WS et al.Airway function in sarcoidosis.Am J Med. 1977; 62: 51-59Abstract Full Text PDF PubMed Scopus (68) Google Scholar, 6Argyropoulou PK Patakas DA Louridas GE Airway function in stage I and Stage II pulmonary sarcoidosis.Respiration. 1984; 46: 17-25Crossref PubMed Scopus (18) Google Scholar, 7Miller A Teirstern AS Jackler I Chuang M Sittzbach LE Airway function in chronic pulmonary sarcoidosis with fibrosis.Am Rev Respir Dis. 1974; 109: 179-189PubMed Google Scholar, 8Kaneko K Sharma OP Airway obstruction in pulmonary sarcoidosis.Bull Europ Physiopath Resp. 1977; 13: 231-240PubMed Google Scholar, 9Dines DE Stubbs SE McDougall JC Obstructive disease of the airways associated with stage I sarcoidosis.Mayo Clin Proc. 1978; 53: 788-791PubMed Google Scholar, 10Dutton RE Renzi PM Lopez-Majano V Renzi GD Airway function in sarcoidosis: smokers vs nonsmokers.Respiration. 1982; 43: 164-173Crossref PubMed Scopus (18) Google Scholar In a study by Levinson et al,5Levinson RS Metzger LF Stanley NN Kelsen SG Altose MD Cherniack WS et al.Airway function in sarcoidosis.Am J Med. 1977; 62: 51-59Abstract Full Text PDF PubMed Scopus (68) Google Scholar abnormal airway function was detected in 18 patients with sarcoidosis, all of whom had restrictive lung disease. In all patients, abnormal airway function was documented by at least one test and usually by multiple tests which included airway conductance, spirometry, frequency dependence of compliance, single breath nitrogen test, and assessment of upstream airway resistance. In a more recent study,6Argyropoulou PK Patakas DA Louridas GE Airway function in stage I and Stage II pulmonary sarcoidosis.Respiration. 1984; 46: 17-25Crossref PubMed Scopus (18) Google Scholar evidence of small airways dysfunction was evident in 39 nonsmoking patients with stage I sarcoidosis and 20 non-smokers with stage II sarcoidosis in whom abnormal test results suggestive of small airflow obstruction were noted in at least 30 percent of stage I patients (range 30-50 percent), and at least 44 percent of stage II patients (range 44-73 percent). Dines et al9Dines DE Stubbs SE McDougall JC Obstructive disease of the airways associated with stage I sarcoidosis.Mayo Clin Proc. 1978; 53: 788-791PubMed Google Scholar described five patients with stage I sarcoidosis associated with airways obstruction, four of whom presented with dyspnea, wheezing and cough. Analysis of flow volume relationships by Miller et al7Miller A Teirstern AS Jackler I Chuang M Sittzbach LE Airway function in chronic pulmonary sarcoidosis with fibrosis.Am Rev Respir Dis. 1974; 109: 179-189PubMed Google Scholar and spirometric measurements by Kaneko and Sharma8Kaneko K Sharma OP Airway obstruction in pulmonary sarcoidosis.Bull Europ Physiopath Resp. 1977; 13: 231-240PubMed Google Scholar indicated the presence of airways obstruction in 75 and 43 percent of patients, respectively, with various stages of sarcoidosis. Kaneko and Sharma8Kaneko K Sharma OP Airway obstruction in pulmonary sarcoidosis.Bull Europ Physiopath Resp. 1977; 13: 231-240PubMed Google Scholar suggested that in a proportion of their cases in whom a low peripheral airway conductance was noted, distorted peripheral airways may be responsible for the flow reduction documented. Dutton et al10Dutton RE Renzi PM Lopez-Majano V Renzi GD Airway function in sarcoidosis: smokers vs nonsmokers.Respiration. 1982; 43: 164-173Crossref PubMed Scopus (18) Google Scholar evaluated airway function in smokers and nonsmokers with sarcoidosis. They suggested that the combination of smoking and sarcoidosis was synergistic, resulting in small airways disease earlier in the course of the condition. Bechel and colleagues11Bechtel JJ Trammell S Dantzker DP Bower JS Airway hyperreactivity in patients with sarcoidosis.Am Rev Respir Dis. 1981; 124: 759-761PubMed Google Scholar evaluated nonspecific bronchial responsiveness to methacholine challenge in 20 patients with sarcoidosis, half of whom demonstrated increased airway reactivity. The responders tended to be more symptomatic with cough and wheeze and had a higher degree of baseline airways obstruction, as well as longer duration of disease. In a study by Presas et al12Presas FM Colomer PR Sanchon BR Bronchial hyperreactivity in fresh stage I sarcoidosis.Ann N Y Acad Sci. 1986; 465: 523-529Crossref PubMed Scopus (16) Google Scholar six of 12 patients with stage I sarcoidosis demonstrated enhanced responsiveness to methacholine. No differences in clinical symptoms or pulmonary function tests distinguished responders from nonresponders in this study. In contrast to the above two studies, Olafsson et al13Olafsson M Simonsson BC Hansson SB Bronchial reactivity in patients with recent pulmonary sarcoidosis.Thorax. 1985; 40: 51-53Crossref PubMed Scopus (24) Google Scholar found that stage I or II sarcoidosis seldom induces airway hyperreactivity in patients with normal spirometry, within one year of diagnosis. The occurrence of severe airflow obstruction in sarcoidosis has rarely been reported.14Zimmerman I Mann N Boeck’s sarcoid: A case of sarcoidosis complicated by pulmonary emphysema and cor pulmonale.Ann Intern Med. 1949; 31: 153-162Crossref PubMed Scopus (8) Google Scholar, 15Harden KA Barthakur A Cavitary lesions in sarcoidosis.Dis Chest. 1959; 35: 607-614Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 16Miller A The vanishing lung syndrome associated with pulmonary sarcoidosis.Br J Dis Chest. 1981; 75: 209-214Abstract Full Text PDF PubMed Scopus (17) Google Scholar In 1949, Zimmerman and Mann14Zimmerman I Mann N Boeck’s sarcoid: A case of sarcoidosis complicated by pulmonary emphysema and cor pulmonale.Ann Intern Med. 1949; 31: 153-162Crossref PubMed Scopus (8) Google Scholar described a 21-year-old black man with sarcoidosis characterized initially by hilar adenopathy and extensive bilateral infiltrates who progressed over ten years to develop severe airflow obstruction, emphysema and cor pulmonale. Autopsy revealed small bullae in various areas of the lung, as well as mild to moderate tubular bronchiectatic changes. Granulomata compatible with sarcoidosis were found in the lung and reticuloendothelial system. The alveolar air spaces varied in size and many were greatly distended with disruption of alveolar septa in some areas. Severe airflow limitation associated with giant bullous emphysema has been reported in three patients with sarcoidosis.15Harden KA Barthakur A Cavitary lesions in sarcoidosis.Dis Chest. 1959; 35: 607-614Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 16Miller A The vanishing lung syndrome associated with pulmonary sarcoidosis.Br J Dis Chest. 1981; 75: 209-214Abstract Full Text PDF PubMed Scopus (17) Google Scholar In two of these patients, resectional surgery (lobectomy) and bullectomies were performed with temporary improvement of symptoms. In both patients, enlarging bullae in the opposite lung were noted following surgery. In one patient, a second thoracotomy and bullectomy was performed16Miller A The vanishing lung syndrome associated with pulmonary sarcoidosis.Br J Dis Chest. 1981; 75: 209-214Abstract Full Text PDF PubMed Scopus (17) Google Scholar with significant palliation of symptoms for 18 months. We have recently reviewed a 65-year-old woman with longstanding sarcoidosis who presented with exertional dyspnea (Lewis MI, unpublished data). Chest radiograph and pulmonary function test results revealed significant hyperinflation and air flow limitation (FEV1 = 0.36 L; FEV1/FVC = 30 percent). She was a nonsmoker with normal levels of α1 antitrypsin who demonstrated progressive deterioration despite maintenance steroid therapy. In a long-term follow-up (minimum four years) of the course of airflow obstruction in patients with sarcoidosis and idiopathic pulmonary fibrosis, Meier-Sydow et al17Meier-Sydow J Rust MG Kappos A Kronenberger H Nerger K Schultze-Werninghaus G The long term course of airflow obstruction in obstructive variants of the fibrotic stage of sarcoidosis and of idiopathic pulmonary fibrosis.Ann N Y Acad Sci. 1986; 465: 515-522Crossref Scopus (2) Google Scholar found lack of progression of airflow obstruction in the majority of patients tested. It is clear, however, that a minority of cases with airway obstructive sarcoidosis may progress considerably, producing in some cases a condition not dissimilar physiologically from an “obliterative bronchiolitis type syndrome.”18Epler GR Colby TV The spectrum of bronchiolitis obliterans.Chest. 1983; 83: 161-162Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar Whether early administration of corticosteroids may prevent or attenuate airway obstructive sarcoidosis is not known. The studies of Benatar and Clark3Benatar SR Clark TJH Pulmonary function in a case of endobronchial sarcoidosis.Am Rev Respir Dis. 1974; 110: 490-496PubMed Google Scholar and Smellie et al19Smellie H Apthorp GH Marshall R The effect of corticosteroid treatment on pulmonary function in sarcoidosis.Thorax. 1961; 16: 87-91Crossref Google Scholar suggest that improvement in pulmonary function is possible. This contrasts with the experience of Olsson et al4Olsson T Bjornstad-Pettersen H Stjernberg NL Bronchostenosis due to sarcoidosis. A cause of atelectasis and airway obstruction simulating pulmonary neoplasm and chronic obstructive pulmonary disease.Chest. 1979; 75: 663-666Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar as well as our own.
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