10 Horwitz 0, Wilbek E, Erickson PA: Epidemiological basis of tuberculosis eradication. Bull WHO 41:95-113, 1969 11 Horwitz 0, Magnus K: Epidemiologic evaluation of chemoprophylaxis against tuberculosis. Am J Epidemiol 99:333-342, 1974 12 Krebs A: The IU AT trial on isoniazid preventive treatment in persons with fibrotic lung lesions. Read before the 23rd International Tuberculosis Conference, Mexico City, Sept 24, 1975 13 Yerushalmy J: The statistical assessment of the variability in observer perception and description of roentgenographic pulmonary shadows. Radio! Clin North Am 7:381-392, 1969 14 Comstock GW: Untreated inactive pulmonary tuberculosis. Public Health Rep 77:461-470, 1962 15 Waaler HT: The definition of high risk groups. Scand J Respir Dis 57: 106-112, 1976
Airway Obstruction in Sarcoidosis Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The lungs are the most commonly involved organs. The granulomata occur typically along lobular septa and are scattered throughout the pulmonary interstitium lining alveolar walls. Occasionally, a granulomatous mass may protrude into an alveolar lumen. Thus, sarcoidosis is considered primarily a disease of the interstitium of the lung. Extensive physiologic studies, with a few exceptions, have emphasized functional changes characteristic of a "restrictive pulmonary disease," ie, reduction in static pulmonary volumes, impaired diffusing capacity (transfer factor), reduced pulmonary compliance, and an abnormal alveolar-arterial oxygen pressure difference; 1•2 however, in these studies, little emphasis was placed on the involvement of the airway in sarcoidosis. It seems surprising, particularly because bronchial or peribronchial granulomata are a common histologic finding in the disease. 3 Indeed, Longcope and Freiman" recognized this fact more than 20 years ago. Does sarcoidosis produce obstruction of the airway? Yes. Indeed, it has been convincingly demonstrated by Levinson et aP The authors of this elegant study examined 18 patients with sarcoidosis with particular reference to the function of their airways. Not only did Levinson et al 5 measure static and dynamic pulmonary volumes, diffusing capacity, and static transpulmonary pressures, but also frequency dependence of dynamic compliance and closing volumes. The function of the airway was abnormal in every patient by at least one of these tests, and nearly always by multiple tests.Using Howvolume curves and the method of nitrogen washout, Miller et al6 have demonstrated the common occurrence of obstruction of the airway in sarcoidosis.
6 EDITORIALS
What is the basis of obstruction of the airway in sarcoidosis? Longcope and Freiman4 suggested that granulomata may compress the lumen of small or large airways and inHuence their function. Levinson et al 5 believed that diminished ratios of the forced expiratory volume in one second over the forced vital capacity ( FEV t! FVC) and abnormal ratios of the closing volume over the vital capacity ( CV /VC) are indicators of dysfunction· of the small airways. This may have resulted either from an effect of granulomata on the airways or from the disruption of the supporting structure around terminal and respiratory bronchioles. In one of the patients of Levinson et al, 5 histologic examination revealed a small airway ( 40p. in diameter) surrounded by granulomatous tissue. Kaneko and Sharma7 studied mechanical properties of the lung in 21 patients; all but one had decreased total lung capacity, and 17 of 21 showed reduced VC in various degrees. To assess whether or not the reduction in the rate of How was out of proportion to the loss of volume, the instantaneous forced expiratory How after 50 percent of the FVC had been exhaled ( FEFSO%) was compared with the predicted value for FEFSO% that was calculated using the patient's FVCs. In nine patients the reduction in FEFSO% was relatively greater than the loss of volume, suggesting obstruction of the airway. When the determining factors of the reduction in How were analyzed, the low conductance of the upstream segment at 50 percent of the FVC, in addition to the decreased VC, could account for the decreased FEFSO%, implying that the How relations were due to distorted peripheral airways. 7 What is the prognostic significance of obstruction of the airway in sarcoidosis? Since the obstruction of the airway is a feature of sarcoidosis, such obstruction may be present in early stages of the disease and may remain undetectable. Indeed, Sharma et al 8 reported increased airway resistance in five of 18 patients with sarcoidosis in whom the chest x-ray film showed only bilateral hilar adenopathy (stage 1). These patients were asymptomatic; however, traditionally, obstruction of the airway is considered to be a manifestation of advanced fibrotic disease with bronchial stenosis and formation of bullae. Studies by Coates and Comroe9 and by McClement et al 10 noted the presence of an increased residual volume and some obstructive changes in some of their patients. Gamain et al 11 have also emphasized the existence of chronic obstructive pulmonary disease in sarcoidosis. Can we prevent the development of advanced obstruction of the airway by treating patients with sarcoidosis early if studies of pulmonary function reveal dysfunction of the airway? It is interesting CHEST, 73: 1, JANUARY, 1978
that Smellie, Apthorp, and MarshalP 2 found that treatment with corticosteroids usually produced an improvement in VC and FEV 1 but had little effect on initially low compliance and a small increase in diffusing capacity. Other authors have concentrated on the effect of therapy with corticosteroids on the diffusing capacity but neglected to study the function of the airway. Studies are needed to investigate the effect of therapy with corticosteroids on the function of the airway at an early stage, in order to see if advance airway-obstructive sarcoidosis can be nipped-in the bud. Om P. Sharma, M.D., F.C.C.P. o Los Angeles
4
5 6 7 8 9
0
Associate Professor of Medicine, School of Medicine, University of Southern California.
10
REFERENCES I Bates DV, Macklem PT, Christie RV: Respiratory Function in Disease (2nd ed). Philadelphia, WB Saunders Co, 1971, pp 287-298 2 Young RCC, Carr TG, Shelton M, et al: Sarcoidosis: Relationship between changes in lung structure and function. Am Rev Respir Dis 95:224-238, 1967 3 Schiessel W, Wurm K, Reindell H: Ergebnisse und
CHEST, 73: 1, JANUARY, 1978
11 12
Bedeutung bronchologischer Untersuchung bei der Lungensarkoidose (Morbus Boeck). Munch Med Wochenschr 103:726-730, 1961 Longcope WT, Freiman DG: A study of sarcoidosis based on a combined investigation of 160 cases, including 30 autopsies from the Johns Hopkins Hospital and the Massachusetts General Hospital. Medicine 31:1, 1952 Levinson RS, Metzger LF, Stanley NN, et al: Airway function in sarcoidosis. Am J Med 62:51-59, 1977 Miller A, Teirstein AS, Jackler I, et al: Airway function in chronic pulmonary sarcoidosis with fibrosis. Am Rev Respir Dis 109:179-189, 1974 Kaneko K, Sharma OP: Airway obstruction in pulmonary sarcoidosis. Bull Eur Physiopathol Respir 13, 1977 Sharma OP, Colp C, Williams MH: Pulmonary function studies in patients with bilateral sarcoidosis of hilar lymph nodes. Arch Intern Med 117:436-440, 1966 Coates EO, Comroe JH: Pulmonary function studies in sarcoidosis. J Clin Invest 30:848, 1951 McClement JH, Renzetti AD, Himmelstein A: Cardiopulmonary function in the pulmonary form of Boeck's sarcoid and its modification by cortisone therapy. Am Rev Tuberc 67: 154, 1953 Gamain B, Coby J, Lambard D, et al: La fonction respiratoire au cours de Ia sarcoidose. Poumon 20:857873, 1964 Smellie H, Apthorp GH, Marshall R: The effects of corticosteroid treatment on pulmonary function in sarcoidosis. Thorax 16:87-91, 1961
EDITORIALS 7
Airway Obstruction in Sarcoidosis Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The lungs are the most commonly involved organs. The granulomata occur typically along lobular septa and are scattered throughout the pulmonary interstitium lining alveolar walls. Occasionally, a granulomatous mass may protrude into an alveolar lumen. Thus, sarcoidosis is considered primarily a disease of the interstitium of the lung. Extensive physiologic studies, with a few exceptions, have emphasized functional changes characteristic of a "restrictive pulmonary disease," ie, reduction in static pulmonary volumes, impaired diffusing capacity (transfer factor), reduced pulmonary compliance, and an abnormal alveolar-arterial oxygen pressure difference; 1•2 however, in these studies, little emphasis was placed on the involvement of the airway in sarcoidosis. It seems surprising, particularly because bronchial or peribronchial granulomata are a common histologic finding in the disease. 3 Indeed, Longcope and Freiman" recognized this fact more than 20 years ago. Does sarcoidosis produce obstruction of the airway? Yes. Indeed, it has been convincingly demonstrated by Levinson et aP The authors of this elegant study examined 18 patients with sarcoidosis with particular reference to the function of their airways. Not only did Levinson et al 5 measure static and dynamic pulmonary volumes, diffusing capacity, and static transpulmonary pressures, but also frequency dependence of dynamic compliance and closing volumes. The function of the airway was abnormal in every patient by at least one of these tests, and nearly always by multiple tests.Using Howvolume curves and the method of nitrogen washout, Miller et al6 have demonstrated the common occurrence of obstruction of the airway in sarcoidosis.
6 EDITORIALS
What is the basis of obstruction of the airway in sarcoidosis? Longcope and Freiman4 suggested that granulomata may compress the lumen of small or large airways and inHuence their function. Levinson et al 5 believed that diminished ratios of the forced expiratory volume in one second over the forced vital capacity ( FEV t! FVC) and abnormal ratios of the closing volume over the vital capacity ( CV /VC) are indicators of dysfunction· of the small airways. This may have resulted either from an effect of granulomata on the airways or from the disruption of the supporting structure around terminal and respiratory bronchioles. In one of the patients of Levinson et al, 5 histologic examination revealed a small airway ( 40p. in diameter) surrounded by granulomatous tissue. Kaneko and Sharma7 studied mechanical properties of the lung in 21 patients; all but one had decreased total lung capacity, and 17 of 21 showed reduced VC in various degrees. To assess whether or not the reduction in the rate of How was out of proportion to the loss of volume, the instantaneous forced expiratory How after 50 percent of the FVC had been exhaled ( FEFSO%) was compared with the predicted value for FEFSO% that was calculated using the patient's FVCs. In nine patients the reduction in FEFSO% was relatively greater than the loss of volume, suggesting obstruction of the airway. When the determining factors of the reduction in How were analyzed, the low conductance of the upstream segment at 50 percent of the FVC, in addition to the decreased VC, could account for the decreased FEFSO%, implying that the How relations were due to distorted peripheral airways. 7 What is the prognostic significance of obstruction of the airway in sarcoidosis? Since the obstruction of the airway is a feature of sarcoidosis, such obstruction may be present in early stages of the disease and may remain undetectable. Indeed, Sharma et al 8 reported increased airway resistance in five of 18 patients with sarcoidosis in whom the chest x-ray film showed only bilateral hilar adenopathy (stage 1). These patients were asymptomatic; however, traditionally, obstruction of the airway is considered to be a manifestation of advanced fibrotic disease with bronchial stenosis and formation of bullae. Studies by Coates and Comroe9 and by McClement et al 10 noted the presence of an increased residual volume and some obstructive changes in some of their patients. Gamain et al 11 have also emphasized the existence of chronic obstructive pulmonary disease in sarcoidosis. Can we prevent the development of advanced obstruction of the airway by treating patients with sarcoidosis early if studies of pulmonary function reveal dysfunction of the airway? It is interesting CHEST, 73: 1, JANUARY, 1978
that Smellie, Apthorp, and MarshalP 2 found that treatment with corticosteroids usually produced an improvement in VC and FEV 1 but had little effect on initially low compliance and a small increase in diffusing capacity. Other authors have concentrated on the effect of therapy with corticosteroids on the diffusing capacity but neglected to study the function of the airway. Studies are needed to investigate the effect of therapy with corticosteroids on the function of the airway at an early stage, in order to see if advance airway-obstructive sarcoidosis can be nipped-in the bud. Om P. Sharma, M.D., F.C.C.P. o Los Angeles
4
5 6 7 8 9
0
Associate Professor of Medicine, School of Medicine, University of Southern California.
10
REFERENCES I Bates DV, Macklem PT, Christie RV: Respiratory Function in Disease (2nd ed). Philadelphia, WB Saunders Co, 1971, pp 287-298 2 Young RCC, Carr TG, Shelton M, et al: Sarcoidosis: Relationship between changes in lung structure and function. Am Rev Respir Dis 95:224-238, 1967 3 Schiessel W, Wurm K, Reindell H: Ergebnisse und
CHEST, 73: 1, JANUARY, 1978
11 12
Bedeutung bronchologischer Untersuchung bei der Lungensarkoidose (Morbus Boeck). Munch Med Wochenschr 103:726-730, 1961 Longcope WT, Freiman DG: A study of sarcoidosis based on a combined investigation of 160 cases, including 30 autopsies from the Johns Hopkins Hospital and the Massachusetts General Hospital. Medicine 31:1, 1952 Levinson RS, Metzger LF, Stanley NN, et al: Airway function in sarcoidosis. Am J Med 62:51-59, 1977 Miller A, Teirstein AS, Jackler I, et al: Airway function in chronic pulmonary sarcoidosis with fibrosis. Am Rev Respir Dis 109:179-189, 1974 Kaneko K, Sharma OP: Airway obstruction in pulmonary sarcoidosis. Bull Eur Physiopathol Respir 13, 1977 Sharma OP, Colp C, Williams MH: Pulmonary function studies in patients with bilateral sarcoidosis of hilar lymph nodes. Arch Intern Med 117:436-440, 1966 Coates EO, Comroe JH: Pulmonary function studies in sarcoidosis. J Clin Invest 30:848, 1951 McClement JH, Renzetti AD, Himmelstein A: Cardiopulmonary function in the pulmonary form of Boeck's sarcoid and its modification by cortisone therapy. Am Rev Tuberc 67: 154, 1953 Gamain B, Coby J, Lambard D, et al: La fonction respiratoire au cours de Ia sarcoidose. Poumon 20:857873, 1964 Smellie H, Apthorp GH, Marshall R: The effects of corticosteroid treatment on pulmonary function in sarcoidosis. Thorax 16:87-91, 1961
EDITORIALS 7
