Respiration JJ: 294-302 (1976)
Early Diagnosis of Interstitial Fibrosis G ildo D. R enzi and V incent L opez -M ajano Hôpital Notre-Dame, Montréal, and Chicago Medical School, Chicago, III.
Key Words. Interstitial • I-'ibrosis • Early diagnosis - Hamman-Rich syndrome Abstract. 2 cases of interstitial fibrosis of the Hamman-Rich type are presented. The patients were symptomatic, but had normal X-rays. They were suspected of having interstitial infiltration by pulmonary function tests. Diagnosis was confirmed by lung biopsy. Pulmonary function tests, especially the study of elastic properties of the lung, can be of primary help in the diagnosis of pulmonary interstitial infil tration and fibrosis when the patient's X-ray is normal.
Hamman-Rich syndrome is a diffuse interstitial fibrosis of unknown etiology. The course of the disease in the original description in 1933 was acute and characterized by pulmonary hypertension, cor pulmonale and respiratory insufficiency [1-3]. However, since then, chronic cases have been described with a diffuse reticular fibrosis on X-ray [4-7]. The earli est radiological manifestation consists of fine reticulation predominantly in the lung bases. In the later stages of the diseases, there is a coarse reti cular and reticular-nodular pattern throughout the lungs with several cys tic spaces 3-10 mm in diameter which create a honeycomb pattern [8], In these advanced stages, there is restrictive disease, decreased diffusion and compliance and hyperventilation at rest. Arterial blood gases show hy poxemia and hypocapnia. The gas exchange may be normal at rest, but abnormalities are ordinarily found on exercise. Because of the pathologi cal changes in the lung, work of breathing is increased and the classical symptom of dyspnea appears.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
Received: January 13, 1975, accepted: July 15, 1975.
R enzi/L opez -M amno
295
Fig. I. L. B. Normal Chest X-ray.
This article presents 2 cases of interstitial fibrosis with a normal chest radiograph and the results of pulmonary function tests were compatible with pulmonary fibrosis. The conclusive diagnosis was established by lung biopsy. Case Report
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
First Case L. B., 37-year-okl female, smoker of 20 cigarettes daily was admitted to the hos pital for investigation of dyspnea. This dyspnea on exertion has been progressive over the past 2 years. She also complained of repeated colds and of a dry cough persistant and non-productive. She also noted a certain asthenia and a loss of weight. She had been investigated 2 years before and X-rays, bronchoscopy and bi lateral bronchography were normal. Physical examination revealed a patient in ap parently good health without cyanosis or clubbing. The heart rate was regular at 80 baets/min. Blood pressure was 135/90, breathing was slightly increased at 22 breaths/min and the temperature was 99 F. The physical examination of the lungs
R enzi / Lopez -M ajano
296
Table I. Lung volumes
VC, 1 RV, 1 CPT, 1 CRF, 1
Patient 1 observed
predicted
observed/ predicted %
2.05 1.51 3.57 2.19
3.33 1.49 4.82 2.54
61.54 101.78 73.96 86.32
Patient 2 observed
predicted
observed/ predicted %
2.53 2.37 4.90 3.00
3.10 1.73 4.83 2.66
81.57 137.13 101.49 122.50
Patient I. Initials: L. B.;sex: F, height: 157.4 cm, weight, 50,7 kg, skin surface: 1.49 m*2. Patient 2. Initials: P. H., sex: F; height: 160 cm, weight: 48 kg, skin surface: 1.47 m2;
Table //. Spirometry Patient 1 observed before bronchodilators after observed predicted bronchodilators FVC, 1 FEV/FVC, % MMFR, l/sec MBC, 1/min
2.05 1.66 80.9 1.62 49.8
3.33 84 3.44 100.2
2.08 1.89 90.6 2.67 56.7
Patient 2 before bronchoobserved dilators after observed predicted bronchodilators 2.49 3.10 2.4 65 1.77 72.0 1.64 65 81.0 2.5 2 1.413 0.95 49 92.4 53.2
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
was normal except for a few rhonchi and rales at the left base. The rest of the phys ical examination was normal. The results of laboratory examination reveal normal results for: (1) hemogram, (2) blood sugar and azotemia, (3) antinuclear antibodies, (4) latex test for rhumatoid arthritis, (5) electrophoresis for protein, (6) sputum test for culture, BK and cytolo gy, (7) electrocardiogram, and (8) intradermo-reactions to tuberculin and histoplasmin. The sedimentation rate was 30 mm/h. The chest X-ray was normal (fig. 1). Pul monary function tests (tables I—III) showed the following abnormalities: lung vol umes (table I) were restrictive and the spirometry (table 11) was at the limit of nor mal except for a slightly decreased MMFR improved after bronchodilators. Gas exchange showed a slight increase of physiological dead space. Steady-state diffu sion was moderately decreased. Arterial blood gases showed slight hypoxemia with out hyperventilation. O, and CO, gradients at rest showed a pattern compatible with
Early Diagnosis of Interstitial Fibrosis
297
Fig. 2. L. B. Lung biopsy showing interstitial fibrosis of the mixed type desqua mative and fibrosing.
high ventilation-perfusion ratios. Static compliance taken from 60 to 80°/o of the ra tio functional residual capacity over total lung capacity showed a low static compli ance and the static pressure volume curves from functional residual capacity to total lung capacity were lowered and shifted to the right and therefore showed a loss of normal elastic properties of the lung. Specific airway resistances were slightly in creased and probably showed slight central airway obstruction (table III). Lung biopsy was performed and the pathologist conclusion was interstitial fibro sis Hamman-Rich of the mixed type, desquamative and fibrosing (fig. 2).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
Second Case P. H. 57-year-old female smoker of 30 cigarettes daily was referred to the Hospi tal for investigation of a pulmonary condition. She complained of a chronic cough productive of white sputum and of dyspnea on exertion. These symptoms had been more severe in the past few weeks. She also noted a slight and irregular fever and also a loss of weight. At the time of admission, the patient was afebrile. Respiration was slightly increased, 24 breaths/min. No cyanosis was noted, no clubbing and no adenopathy. The heart rate was regular at 80 beats/min. No murmur was heard. Blood pressure was 140/90. Physical examination of the chest showed a slight de crease in expansion. Breath sounds were slightly decreased bilaterally and crepitant rales were heard at both bases. The rest of physical examination was not contributo ry. The chest X-ray was normal except for moderate hyperinflation (fig. 3).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
Fin. 4. P. H. I.ung biopsy showing fibrosis and intra-alveolar desquamation. *7 w
Early Diagnosis of Interstitial Fibrosis
299
Table III. Ventilation, diffusion, blood gases, gradients and shunt, lung compliance and airway resistance Patient 1 observed
predicted
Patient 2 observed
predicted
0.496 15 7.45 41.01
34.29
441 16 7.06 48.74
31.32
8.28
12.47
10.52
16.83
Ventilation VT, 1 F, rpm VE, l/min V d/V t , %
Diffusion, DLCO (SS2 ), ml CO/min/mm Hg Blood gases PaO, mm Hg SAT.O2 , % PaCC>2 , mm Hg pH Heos, mEq/1
78 93.5 41 7.41 25.2
>85 97 38-42 7.38-7.42 23-25
68 90 39 7.39 23.00
>85 97 38-42 7.38-7.42 23-25
23 12.8
Early Diagnosis of Interstitial Fibrosis G ildo D. R enzi and V incent L opez -M ajano Hôpital Notre-Dame, Montréal, and Chicago Medical School, Chicago, III.
Key Words. Interstitial • I-'ibrosis • Early diagnosis - Hamman-Rich syndrome Abstract. 2 cases of interstitial fibrosis of the Hamman-Rich type are presented. The patients were symptomatic, but had normal X-rays. They were suspected of having interstitial infiltration by pulmonary function tests. Diagnosis was confirmed by lung biopsy. Pulmonary function tests, especially the study of elastic properties of the lung, can be of primary help in the diagnosis of pulmonary interstitial infil tration and fibrosis when the patient's X-ray is normal.
Hamman-Rich syndrome is a diffuse interstitial fibrosis of unknown etiology. The course of the disease in the original description in 1933 was acute and characterized by pulmonary hypertension, cor pulmonale and respiratory insufficiency [1-3]. However, since then, chronic cases have been described with a diffuse reticular fibrosis on X-ray [4-7]. The earli est radiological manifestation consists of fine reticulation predominantly in the lung bases. In the later stages of the diseases, there is a coarse reti cular and reticular-nodular pattern throughout the lungs with several cys tic spaces 3-10 mm in diameter which create a honeycomb pattern [8], In these advanced stages, there is restrictive disease, decreased diffusion and compliance and hyperventilation at rest. Arterial blood gases show hy poxemia and hypocapnia. The gas exchange may be normal at rest, but abnormalities are ordinarily found on exercise. Because of the pathologi cal changes in the lung, work of breathing is increased and the classical symptom of dyspnea appears.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
Received: January 13, 1975, accepted: July 15, 1975.
R enzi/L opez -M amno
295
Fig. I. L. B. Normal Chest X-ray.
This article presents 2 cases of interstitial fibrosis with a normal chest radiograph and the results of pulmonary function tests were compatible with pulmonary fibrosis. The conclusive diagnosis was established by lung biopsy. Case Report
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
First Case L. B., 37-year-okl female, smoker of 20 cigarettes daily was admitted to the hos pital for investigation of dyspnea. This dyspnea on exertion has been progressive over the past 2 years. She also complained of repeated colds and of a dry cough persistant and non-productive. She also noted a certain asthenia and a loss of weight. She had been investigated 2 years before and X-rays, bronchoscopy and bi lateral bronchography were normal. Physical examination revealed a patient in ap parently good health without cyanosis or clubbing. The heart rate was regular at 80 baets/min. Blood pressure was 135/90, breathing was slightly increased at 22 breaths/min and the temperature was 99 F. The physical examination of the lungs
R enzi / Lopez -M ajano
296
Table I. Lung volumes
VC, 1 RV, 1 CPT, 1 CRF, 1
Patient 1 observed
predicted
observed/ predicted %
2.05 1.51 3.57 2.19
3.33 1.49 4.82 2.54
61.54 101.78 73.96 86.32
Patient 2 observed
predicted
observed/ predicted %
2.53 2.37 4.90 3.00
3.10 1.73 4.83 2.66
81.57 137.13 101.49 122.50
Patient I. Initials: L. B.;sex: F, height: 157.4 cm, weight, 50,7 kg, skin surface: 1.49 m*2. Patient 2. Initials: P. H., sex: F; height: 160 cm, weight: 48 kg, skin surface: 1.47 m2;
Table //. Spirometry Patient 1 observed before bronchodilators after observed predicted bronchodilators FVC, 1 FEV/FVC, % MMFR, l/sec MBC, 1/min
2.05 1.66 80.9 1.62 49.8
3.33 84 3.44 100.2
2.08 1.89 90.6 2.67 56.7
Patient 2 before bronchoobserved dilators after observed predicted bronchodilators 2.49 3.10 2.4 65 1.77 72.0 1.64 65 81.0 2.5 2 1.413 0.95 49 92.4 53.2
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
was normal except for a few rhonchi and rales at the left base. The rest of the phys ical examination was normal. The results of laboratory examination reveal normal results for: (1) hemogram, (2) blood sugar and azotemia, (3) antinuclear antibodies, (4) latex test for rhumatoid arthritis, (5) electrophoresis for protein, (6) sputum test for culture, BK and cytolo gy, (7) electrocardiogram, and (8) intradermo-reactions to tuberculin and histoplasmin. The sedimentation rate was 30 mm/h. The chest X-ray was normal (fig. 1). Pul monary function tests (tables I—III) showed the following abnormalities: lung vol umes (table I) were restrictive and the spirometry (table 11) was at the limit of nor mal except for a slightly decreased MMFR improved after bronchodilators. Gas exchange showed a slight increase of physiological dead space. Steady-state diffu sion was moderately decreased. Arterial blood gases showed slight hypoxemia with out hyperventilation. O, and CO, gradients at rest showed a pattern compatible with
Early Diagnosis of Interstitial Fibrosis
297
Fig. 2. L. B. Lung biopsy showing interstitial fibrosis of the mixed type desqua mative and fibrosing.
high ventilation-perfusion ratios. Static compliance taken from 60 to 80°/o of the ra tio functional residual capacity over total lung capacity showed a low static compli ance and the static pressure volume curves from functional residual capacity to total lung capacity were lowered and shifted to the right and therefore showed a loss of normal elastic properties of the lung. Specific airway resistances were slightly in creased and probably showed slight central airway obstruction (table III). Lung biopsy was performed and the pathologist conclusion was interstitial fibro sis Hamman-Rich of the mixed type, desquamative and fibrosing (fig. 2).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
Second Case P. H. 57-year-old female smoker of 30 cigarettes daily was referred to the Hospi tal for investigation of a pulmonary condition. She complained of a chronic cough productive of white sputum and of dyspnea on exertion. These symptoms had been more severe in the past few weeks. She also noted a slight and irregular fever and also a loss of weight. At the time of admission, the patient was afebrile. Respiration was slightly increased, 24 breaths/min. No cyanosis was noted, no clubbing and no adenopathy. The heart rate was regular at 80 beats/min. No murmur was heard. Blood pressure was 140/90. Physical examination of the chest showed a slight de crease in expansion. Breath sounds were slightly decreased bilaterally and crepitant rales were heard at both bases. The rest of physical examination was not contributo ry. The chest X-ray was normal except for moderate hyperinflation (fig. 3).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 1:52:23 AM
Fin. 4. P. H. I.ung biopsy showing fibrosis and intra-alveolar desquamation. *7 w
Early Diagnosis of Interstitial Fibrosis
299
Table III. Ventilation, diffusion, blood gases, gradients and shunt, lung compliance and airway resistance Patient 1 observed
predicted
Patient 2 observed
predicted
0.496 15 7.45 41.01
34.29
441 16 7.06 48.74
31.32
8.28
12.47
10.52
16.83
Ventilation VT, 1 F, rpm VE, l/min V d/V t , %
Diffusion, DLCO (SS2 ), ml CO/min/mm Hg Blood gases PaO, mm Hg SAT.O2 , % PaCC>2 , mm Hg pH Heos, mEq/1
78 93.5 41 7.41 25.2
>85 97 38-42 7.38-7.42 23-25
68 90 39 7.39 23.00
>85 97 38-42 7.38-7.42 23-25
23 12.8
