Portal de Periódicos da CAPES

Chronic Obstructive Pulmonary Disease following Idiopathic Pulmonary Fibrosis

1980; Elsevier BV; Volume: 77; Issue: 4 Linguagem: Inglês

10.1378/chest.77.4.473

1931-3543

D.S. McCarthy, David N. Ostrow, Earl S. Hershfield,

Sarcoidosis and Beryllium Toxicity Research

The rapid development of irreversible airflow obstruction in two nonsmoking women who recovered from acute idiopathic pulmonary fibrosis is discussed. Pulmonary fibrosis was diagnosed clinically and by lung biopsy. Recovery both clinically and radiologically was complete. Several pulmonary function studies in both patients showed a typical restrictive pattern (reduced lung volumes and carbon dioxide diffusing capacity, normal FEV1/FVC ratio). Within one year both patients exhibited an obstructive pattern of dysfunction (hyperinflation, gas trapping, reduced airflow measurements). These patients illustrated irreversible airway obstruction following recovery from the restrictive stage of pulmonary fibrosis. The inflammatory process in idiopathic pulmonary fibrosis involves the alveoli as well as the bronchioles.1Hamman L Rich AR Acute diffuse interstitial fibrosis of the lungs.Bull Johns Hopkins Hospital. 1944; 74: 177-212Google Scholar Fulmer et al2Fulmer JD Roberts WC Von bal ER et al.Small airways in idiopathic pulmonary fibrosis.J Clin Invest. 1977; 60: 595-610Crossref PubMed Scopus (102) Google Scholar reported that 17 of 18 patients with this diagnosis had pathologic and physiologic evidence of bronchiolar disease. Other authors have reported small airways disease in idiopathic pulmonary fibrosis3Ostrow D Cherniack RM Resistance to airflow in patients with diffuse interstitial lung disease.Am Rev Respir Dis. 1973; 108: 205-210PubMed Google Scholar and other idiopathic disease involving the lung parenchyma such as pulmonary sarcoidosis4Levinson RS Metger IF Stanley NN et al.Airway function in sarcoidosis.Am J Med. 1977; 62: 51-59Abstract Full Text PDF PubMed Scopus (74) Google Scholar, 5McCarthy DS Sigurdson M Lung function in pulmonary sarcoidosis.Irish J Med Sci. 1978; 147: 413Crossref PubMed Scopus (5) Google Scholar and progressive systemic sclerosis.6Guttadauria M Ellman H Emmanuel A Pulmonary function in scleroderma.Arthritis Rheum. 1977; 20: 1071Crossref PubMed Scopus (63) Google Scholar, 7Bjerhe RD Tashkin DP Clements PJ et al.Small airways in progressive systemic sclerosis (PSS).Am J Med. 1979; 66: 201-209Abstract Full Text PDF PubMed Scopus (49) Google Scholar For commentary, see page 470 This report describes the rapid development of irreversible airflow obstruction in two middle-aged nonsmoking women who had recovered clinically and radiologically from acute idiopathic pulmonary fibrosis (Hamman-Rich disease). A 58-year-old housewife was admitted to the hospital with an eight-week history of progressive cough productive of 3* cup mucopurulent sputum per day, feverishness and increasing shortness of breath and fatigue with a weight loss of 3.5 kg. There was no history of chest pain, wheezing, swelling of ankles or joints. Past history was non-contributory. The patient did not smoke, had no allergies, and had been a housewife all her adult life. There was no known exposure Jo noxious inhalants. On physical examination, the patient was found to be of average nutrition, temperature 38.8 °C, pulse rate 108, respirations 24/min, blood pressure 110/70 mm Hg. The trachea was deviated to the right; there was no clubbing of digits. Chest movements and air entry were diminished over the right lung, and there was dullness to percussion and increased tactile vocal fremitus on the right side. Mid and late inspiratory crackles were present over both lungs, especially the lower lobes. No clinical evidence of airways obstruction was found. Other systems were normal. The roentgenogram taken on admission showed bilateral lung infitrations, especially on the right side. A chest film had been taken 15 months earlier because of unrelated problems but showed normal findings. Because of difficulty in establishing a diagnosis, lung biopsy was performed through a small right thoracotomy. On inspection the lung was unremarkable and a biopsy was taken from the right upper lobe. The biopsy revealed diffuse disease with interstitial fibrosis and pronounced epithelial hyperplasia of the alveolar walls. There were numerous subepithelial collections of foamy macrophages and many free alveolar phagocytes (Fig 1A). Several wide bands of fibrosis were seen and vascular sclerosis was pronounced. The respiratory bronchioli showed changes of obliterative bronchiolitis (Fig 1B). No granulomata were seen. The patient was treated with antibiotics, but showed no improvement. Following the lung biopsy, she was given prednisone, 40 mg/day. On this treatment, the clinical symptoms subsided and the functional abnormalities reversed (Table 1, Table 2, Figure 3, Figure 4) so that after one month of treatment, there were normal findings on chest radiograph and she felt completely well. The dosage of corticosteroids was gradually reduced and finally stopped after three months without untoward effects or recurrence of lung disease.Table 1Pulmonary Function TestsInitial PresentationOne Month Later7-12 Months LaterPatient 1TLC (L)2.07 (49)*Values in parentheses are percent predicted4.02 (95)7.53 (153)FRC (L)1.34 (61)2.92 (133)5.03 (194)RV (L)0.75 (53)1.64 (116)3.43 (203)FVC (L)1.51 (54)2.65 (95)3.52 (109)FEV1.0/FVC848055MMEFR (L/sec)1.13 (49)2.70 (114)1.20 (51)DLco (ml/min/mm Hg)7.0 (59)11.6 (98)10 (83)Patient 2TLC (L)2.93 (62)3.96 (84)6.35 (135)FRC (L)1.83 (62)2.58 (97)3.78 (142)RV (L)1.45 (82)1.87 (106)3.24 (183)FVC (L)1.42 (48)2.0 (68) .3.15 (107)FEV1.0/FVC807565MMEFR (L/sec)1.20 (34)2.7 (77)1.45 (37)DLco (ml/min/mm Hg)8.1 (69)9.24 (79)11.42 (97)* Values in parentheses are percent predicted Open table in a new tab Table 2Gas ExchangeInitial PresentationOne Month Later7–12 Months LaterPatient 1PaO2 (mm Hg)67 (60)*Values in parentheses are exercise values86 (83)82 (78)PaCO2 (mm Hg)38 (40)39 (40)36 (32)A‐aDO2 (mm Hg)32 (37)11 (20)23 (30)Shunt (on 100% O2)1367Patient 2PaO2 (mm Hg)51 (49)74 (74)79 (84)PaCO2 (mm Hg)29 (25)31 (33)36 (37)A‐aDO2 (mm Hg)57 (64)39 (38)20 (18)Shunt (on 100% O2)2594* Values in parentheses are exercise values Open table in a new tab Figure 4The relationship of maximal expiratory flow (Vmax) to static recoil pressure of the lungs (Pst) in the two patients. Mean ± 1 SD values of normal subjects are shown for comparison (…) at 50, 70 and 90 percent of TLC predicted. Patient 1…, patient 2…, ○ initial presentation, □ one month later, ▪ 7-12 months later.View Large Image Figure ViewerDownload (PPT) Her subsequent course was uneventful until about seven months later when she noted return of shortness of breath and wheezing. On examination, there was evidence of airflow obstruction in that the lungs were hyperinflated, breath sounds were bronchovesicular in character and scattered wheezes were heard throughout the lung fields especially during the expiratory phase of respiration. Chest radiograph confirmed hyperinflation as indicated by translucent lung fields, low flat diaphragm shadows and increased retrosternal space. Bullae were not seen. The lung function studies showed typical changes of an obstructive pattern of disease (Table 1, Table 2, Figure 3, Figure 4). A 61-year-old housewife was admitted to the hospital with a six-week history of feverishness, shortness of breath and weight loss (6 kg). There was no history of wheezing, chest pain or joint swelling. The patient did not smoke, had no allergies and had been a housewife throughout her adult life. There was no history of exposure to unusual concentrations of organic dusts. Prior to her current illness she had been completely well and denied any previous respiratory symptoms. On physical examination, the patient was found to be febrile, (temperature 38°C), tachypneic, respiratory rate 22/min, with a dry, repetitive cough, especially on taking deep breaths. Examination of the chest revealed bilateral basal dullness, increased tactile vocal fremitus and showers of late inspiratory crackles throughout the lung fields, but especially over the lower lobes. There was no clubbing of digits and clinical signs of airflow obstruction were not elicited. The balance of findings on physical examination were normal. Chest radiograph on admission showed diffuse, bilateral reticulonodular shadowing involving predominantly the lower lobes and especially the right lower lobe (Fig 2). Lung biopsy was performed through a small right anterior thoracotomy. The tissue showed marked proliferation of the alveolar lining cells and many mononuclear cells free within the alveolar spaces. Pulmonary arterioles were prominent and some showed sclerosis. No granulomata were present. There was little collagen tissue deposited in the alveolar walls. Fibrous tissue was noted within small bronchi in areas indicating endobronchiolar fibrosis. The management and clinical course in this patient was similar to Case 1. The patient was treated with antibiotics without improvement, and, following lung biopsy, she was then placed on prednisone 40 mg/day. There was marked clinical, radiologic and functional improvement after four weeks (Table 1, Table 2, Figure 3, Figure 4). We were unable to withdraw corticosteroid treatment completely, as the patient complained of feeling unwell and short of breath when on less than 5 mg of prednisone per day. After about 12 months, she noted wheezing which did not clear on increasing the dosage of corticosteroids. Clinical examination at this time revealed signs of hyperinflation and scattered expiratory rhonchi and wheezes. Chest radiograph demonstrated the features of hyperinflation, low flat diaphragm and increased retrosternal space and the physiologic measurements confirmed that the patient now had an obstructive pattern of disease (Table 1, Table 2, Figure 3, Figure 4). Both patients had elevated peripheral blood eosinophil counts–2,400 and 2,300/cu mm in Case 1 and 1,300 and 900/cu mm in Case 2. Serum was negative for antinuclear factor, rheumatoid factor and LE cells. Both patients had normal alpha1-antitrypsin levels and negative serologic tests for the following viruses: adenovirus, respiratory syncytial virus, para-influenza 1, para-influenza 2, para-influenza 3, influenza A, influenza B and Mycoplasma pneumonia. Lung biopsy material and cultures of sputum were negative for bacteria, mycobacteria and fungus growth. Elastic recoil of the lungs was determined with the subjects seated, as described by Milic-Emili et al.8Milic-Emili I Mead I Turner M et al.Improved technique for estimating pleural pressure from esophageal balloons.J Appl Physiol. 1961; 19: 207-211Google Scholar Esophageal pressure was recorded from a 10 cm thin-walled latex balloon containing 0.5 ml of air positioned in the lower third of the esophagus and connected to one side of a Statham differential strain gauge (No 5). The other side was connected to a lateral pressure tap in the mouthpiece. Airflow was measured by a heated Fleisch pneumotachometer (No 3) and this signal integrated to obtain volume. Transpulmonary pressure, flow and volume were recorded simultaneously on a Beckman multichannel recorder. Static transpulmonary pressure-volume relationships of the lungs were measured during interrupted vital capacity expirations. The interruptions were accomplished by occluding the mouthpiece. Maximal expired flow-volume curves were measured from a forced expired vital capacity using an automated wedge spirometer.9Cherniack RM Raber MB Normal standards for ventilatory function using an automated wedge spirometer.Am Rev Respir Dis. 1972; 106: 38-46Crossref PubMed Scopus (230) Google Scholar Functional residual capacity (FRC) was measured in a constant pressure body Plethysmograph according to the method of Du Bois.10Du Bois AB Botelho SY Comroe Jr, JH A new method for measuring airway resistance in man using a body Plethysmograph: values in normal subjects and in patients with respiratory disease.J Clin Invest. 1956; 35: 327-335Crossref PubMed Scopus (698) Google Scholar Expiratory reserve volume was subtracted to obtain residual volume (RV) and vital capacity (VC) was added to obtain total lung capacity (TLC). Diffusing capacity for carbon monoxide (Deo) was measured by the steady-state end-tidal technique.10Du Bois AB Botelho SY Comroe Jr, JH A new method for measuring airway resistance in man using a body Plethysmograph: values in normal subjects and in patients with respiratory disease.J Clin Invest. 1956; 35: 327-335Crossref PubMed Scopus (698) Google Scholar We used predicted values for lung volumes established by Goldman et al,12Goldman HI Becklake MR Respiratory function tests: normal values at medium altitudes and the prediction of normal results.Am Rev Tuberc Pulm Dis. 1959; 79: 457-467PubMed Google Scholar for forced vital capacity (FVC) by Cherniack et al9Cherniack RM Raber MB Normal standards for ventilatory function using an automated wedge spirometer.Am Rev Respir Dis. 1972; 106: 38-46Crossref PubMed Scopus (230) Google Scholar and for carbon monoxide diffusion by Bates et al.11Bates DV Boucot NG Dormer AE The pulmonary diffusing capacity in normal subjects.J Physiol. 1971; 129: 237-252Crossref Scopus (88) Google Scholar Normal values for lung mechanics were generated from 24 matched normal nonsmoking subjects in our own laboratories (unpublished). Pressure flow plots to estimate upstream resistance (Rus) were constructed according to the method of Mead et al13Mead J Turner JM Macklem PT et al.Significance of the relationship between lung recoil and maximum expiratory flow.J Appl Physiol. 1967; 22: 95-108Crossref PubMed Scopus (654) Google Scholar to investigate whether flows obtained were appropriate for the transpulmonary pressure which was driving flow at given lung volumes. During the acute stage of the disease a typical restrictive pattern of lung function abnormality was found as indicated by reduced lung volumes and carbon monoxide diffusing capacity and a normal FEV1.0/FVC ratio. (Table 1) Following clinical and radiologic recovery, lung volumes, flow rates and diffusing capacity returned to near normal predicted values. However, 7 to 12 months later an obstructive pattern of dysfunction was found, as indicated by hyperinflation, increased gas trapping and reduced airflow measurements which were unresponsive to sympathicomimetic bronchodilators. (Table 1) Values on gas exchange studies at rest and on exercise are similar to those commonly found in patients with restrictive, normal and obstructive patterns of lung function abnormality respectively (Table 2). The lung pressure-volume data are compatible with the patterns of lung function abnormality suggested. During the acute stage of disease, lung volumes were reduced and lung elastic recoil at any given lung volume was increased. Following recovery, the pressure volume relationships of the lungs were virtually normal while the curves 6-12 months later were shifted up and to the left indicating increased lung volumes and loss of lung elastic recoil at any given lung volume (Fig 3). Pressure-flow relationships (rus) at 50, 70 and 90 percent of TLC are shown in Figure 4. It can be appreciated that the data obtained when the patients first presented are displaced downwards and to the right indicating increased resistance to airflow in the small airways upstream from the equal pressure point as outlined by the concepts of Mead et al.13Mead J Turner JM Macklem PT et al.Significance of the relationship between lung recoil and maximum expiratory flow.J Appl Physiol. 1967; 22: 95-108Crossref PubMed Scopus (654) Google Scholar It can be readily appreciated that in the restrictive stage the patients show evidence of small airway disease. Following clinical recovery the pressure flow relationships were within normal limits. Six to 12 months later the pressure-flow curves were shifted towards the origin coincident with the normal relationships. This indicates that the reduced flow rates were predominantly due to decreased elastic recoil. It is becoming more widely recognized that patients with interstitial lung disease have evidence of airflow abnormality if appropriate tests are applied.2Fulmer JD Roberts WC Von bal ER et al.Small airways in idiopathic pulmonary fibrosis.J Clin Invest. 1977; 60: 595-610Crossref PubMed Scopus (102) Google Scholar, 3Ostrow D Cherniack RM Resistance to airflow in patients with diffuse interstitial lung disease.Am Rev Respir Dis. 1973; 108: 205-210PubMed Google Scholar Some patients with pulmonary sarcoidosis have reduced airflow,4Levinson RS Metger IF Stanley NN et al.Airway function in sarcoidosis.Am J Med. 1977; 62: 51-59Abstract Full Text PDF PubMed Scopus (74) Google Scholar, 5McCarthy DS Sigurdson M Lung function in pulmonary sarcoidosis.Irish J Med Sci. 1978; 147: 413Crossref PubMed Scopus (5) Google Scholar while patients with progressive systemic sclerosis have airway involvement.6Guttadauria M Ellman H Emmanuel A Pulmonary function in scleroderma.Arthritis Rheum. 1977; 20: 1071Crossref PubMed Scopus (63) Google Scholar, 7Bjerhe RD Tashkin DP Clements PJ et al.Small airways in progressive systemic sclerosis (PSS).Am J Med. 1979; 66: 201-209Abstract Full Text PDF PubMed Scopus (49) Google Scholar In some patients with extrinsic allergic alveolitis, a condition reminiscent of chronic obstructive lung disease, has been described.14Seal RME Hapke EJ Thomas GO et al.The pathology of the acute and chronic stages of farmer's lung.Thorax. 1968; 23: 469-489Crossref PubMed Scopus (146) Google Scholar, 15Warren CPW Tse KS Cherniack RM Mechanical properties of the lungs in extrinsic allergic alveolitis.Thorax. 1978; 33: 315-321Crossref PubMed Scopus (32) Google Scholar Ostrow et al3Ostrow D Cherniack RM Resistance to airflow in patients with diffuse interstitial lung disease.Am Rev Respir Dis. 1973; 108: 205-210PubMed Google Scholar described increased airflow resistance in patients with diffuse interstitial lung disease, seven of whom had a diagnosis of idiopathic pulmonary fibrosis. More recently, Fulmer et al2Fulmer JD Roberts WC Von bal ER et al.Small airways in idiopathic pulmonary fibrosis.J Clin Invest. 1977; 60: 595-610Crossref PubMed Scopus (102) Google Scholar reported that 17 of 18 patients with idiopathic pulmonary fibrosis had pathologic changes at the level of the bronchioles, described as peribronchiolar fibrosis, peribronchiolar inflammation or bronchiolitis. Sixty-seven percent (12 of 18 patients) had physiologic evidence of small airway disease as evidenced by frequency, dependence of compliance or abnormal maximum expiratory flow-volume curves. A chronic obstructive pattern of ventilatory abnormality was not observed possibly because follow-up studies at 6-12 months were not reported. Of special interest in the context of this report was the patient reported by Sohko and Bedell16Sohko JA Bedell GW A severe stable obstructive defect in the airways in primary pulmonary histiocytosis.Chest. 1979; 75: 505-507Google Scholar in whom severe, stable airflow obstruction developed following recovery from the pulmonary infiltrative stage of primary pulmonary histiocytosis. Inflammatory involvement of the bronchioles has been advanced to explain increased airflow resistance in patients with idiopathic pulmonic fibrosis.2Fulmer JD Roberts WC Von bal ER et al.Small airways in idiopathic pulmonary fibrosis.J Clin Invest. 1977; 60: 595-610Crossref PubMed Scopus (102) Google Scholar, 3Ostrow D Cherniack RM Resistance to airflow in patients with diffuse interstitial lung disease.Am Rev Respir Dis. 1973; 108: 205-210PubMed Google Scholar Narrowing and stenosis of small airways were noted in the original description by Hamman and Rich.1Hamman L Rich AR Acute diffuse interstitial fibrosis of the lungs.Bull Johns Hopkins Hospital. 1944; 74: 177-212Google Scholar In the present study, pathologic changes were noted in the alveolar walls and in the bronchioles (Fig 1A, IB). These changes could account for both the restrictive pattern of ventilatory function and evidence of airflow obstruction. Following corticosteroid therapy, there was apparent resolution of the clinical disease and normalization of the lung volumes, elastic recoil, gas exchange and airflow measurements. However, in 6 to 12 months, an obstructive pattern of ventilatory abnormality ensued with increased lung volumes (hyperinflation and increased gas trapping) and reduced airflow measurements (Table 1, Table 2, Figure 3, Figure 4). It seems reasonable to postulate that some patients who apparently recover from the acute stage of idiopathic pulmonary fibrosis and small airway inflammation may later develop the clinical, radiologic and physiologic features of chronic obstructive lung disease. The underlying mechanism may be similar to that suggested by Hogg et al17Hogg JC Macklem PT Thurlbeck WM Site and nature of airways obstruction in chronic obstructive lung disease.N Engl J Med. 1968; 278: 1355-1360Crossref PubMed Scopus (1012) Google Scholar in chronic obstructive lung disease where inflammation of small airways was found early in the course of disease. A similar mechanism was discussed in the case report of Sohko and Bedell.16Sohko JA Bedell GW A severe stable obstructive defect in the airways in primary pulmonary histiocytosis.Chest. 1979; 75: 505-507Google Scholar Seal et al14Seal RME Hapke EJ Thomas GO et al.The pathology of the acute and chronic stages of farmer's lung.Thorax. 1968; 23: 469-489Crossref PubMed Scopus (146) Google Scholar and Warren et al15Warren CPW Tse KS Cherniack RM Mechanical properties of the lungs in extrinsic allergic alveolitis.Thorax. 1978; 33: 315-321Crossref PubMed Scopus (32) Google Scholar reported similar findings in chronic extrinsic allergic alveolitis. At the outset, the patients described in this report demonstrated the characteristic clinical, radiologic, physiologic and morphologic feaures of idiopathic pulmonary fibrosis.1Hamman L Rich AR Acute diffuse interstitial fibrosis of the lungs.Bull Johns Hopkins Hospital. 1944; 74: 177-212Google Scholar, 2Fulmer JD Roberts WC Von bal ER et al.Small airways in idiopathic pulmonary fibrosis.J Clin Invest. 1977; 60: 595-610Crossref PubMed Scopus (102) Google Scholar, 3Ostrow D Cherniack RM Resistance to airflow in patients with diffuse interstitial lung disease.Am Rev Respir Dis. 1973; 108: 205-210PubMed Google Scholar Neither patient had a previous history of lung disease nor abnormal chest radiograph. The role of cigarette smoking can be excluded, as neither patient had ever smoked. Despite intensive investigation it was not possible to establish an alternative diagnosis. It thus appears that all abnormalities of lung function detected in the course of this investigation are likely to be the result of idiopathic pulmonary fibrosis. In conclusion, these two patients illustrate that a clinical picture of moderately severe irreversible airflow obstruction may follow apparent resolution of the acute restrictive stage of idiopathic pulmonary fibrosis.