bacteria should be considered in the workup of patients with suspected hypersensitivity pneumonitis. It is emphasized that a majority of humdifier fluids will be positive for thermotolerant bacteria when cultured. 2 For example, in our survey of humidifiers from Denver physicians' homes, 7/9 were culture-positive for thermotolerant bacteria, but not Actinomycetes. Under appropriate conditions of host exposure and with an exaggerated immunologic response ( s), type as yet determined, these bacterial aerosols can produce hypersensitivity pneumonitis. REFERENCES
1 Banaszak EF, Thiede WH, Fink JN: Hypersensitivity pneumonitis due to contaminated air conditioner. N Eng! J Med 283:271-276, 1970 2 Banaszak EF, Barboriak J, Fink J, et al: Epidemiological studies relating thermophilic fungi and hypersensitivity lung syndromes. Am Rev Resp Dis 110:585-591, 1974 FIGURE 1. Diffuse bilateral interstitial changes seen at both bases, slightly more prominent on the left in case 1 at time of diagnosis.
Desquamative Interstitial Pneumonia following Chronic Nitrofurantoin Therapy*
filtrates, more prominent in the bases (Fig 1). Pulmonary function studies were characterized by a restrictive defect and moderate impairment of gas transfer (Table 1). Lung biopsies examined by light microscopy in two patients were characterized by large numbers of intraalveolar mononuclear cells and other pathologic changes consistent with desquamative interstitial pneumonia (DIP), 9 in contrast to the nonspecific fibrosing interstitial pneumonitis previously reported by others (Fig 2) . The appearance of one biopsy studied by electron microscopy was similar to that described for DIP. Hyperplastic cells lining alveolar septa had microvilli and contained lamellar inclusions typical of granular (type II) pneumocytes; intra-alveolar cells had the morphologic features of macrophages (Fig 3) , including long pseudopodia, numerous electron-dense cytoplasmic granules, and only rarely a lamellar inclusion. Immunofluorescence studies on one biopsy showed deposits of IgE and C3 component of complement within interstitial cells. By in vitro studies, nitrofurantoin failed to induce lymphoblast transformation or release of
Roger C. Bone, M.D.;•• John Wolfe, M.D.;t Richard E. Sobonya, M.D.** Gerald R. Kerby, M.D.;t Daniel Stechschulte, M.D.;t William E. Ruth, M.D.;§ and Maura Welchjj
hirteen cases of pulmonary fibrosis attributed to T chronic nitrofurantoin use have been described previously .1-8 Three additional patients who developed diffuse interstitial lung disease during chronic (two to five years) nitrofurantoin therapy have been studied. Clinical findings included exertional dyspnea and basilar rales. Chest roentgenograms demonstrated interstitial in*From the Departments of Internal Medicine, Pathology and Oncology, University of Kansas Medical Center, Kansas City, Kansas. Supported in part by NIH Training grants 173701, 5-T01B-M01783, and Hospital Research grant 712227. 0 0 Assistant Professor. tPulmonary Fellow. tAssociate Professor. §Professor. [!Medical Student.
Table I -Selected PulmoiUJry Function Before and After Treatment of Nitrofurantoin LuRfi Di.ea•e*
Patient No. 1 Before After
Measurement
Patient No. 2 Before After
Patient No. 3 Before After
Forced Vital Capacity, Liter
1.70 (67%)
2.00 (79%)
3.00 (65%)
4.55 (99%)
2.36 (59%)
4.16 (106%)
Total Lung Capacity, Liter
3.67 (100%)
3.50 (96%)
4.79 (80%)
6.15 (103%)
4.58 (79%)
6.30 (108%)
DLCo, t ml/min/mm Hg
12 (70%)
11.4 (67%)
16.5 (65%)
18.2 (72%)
11.3 (61%)
18.2 (98%)
Pa01, mm Hg
76
82
66
83
80
70t
83
84t
PaCO,, mm Hg
34
41
36
34
38
44i
34
42t
pH, units
7.43
7.34
7.44
7.52
7.38
7.52
*Patient No. 1 treated by discontinuing nitrofurantoin. Patients No. 2 and No. 3 treated by discontinuing nitrofurantoin and beginning corticosteroids tSingle breath diffusion tExercise blood gas values Parentheses = percent predicted value
296
18TH ASPEN CONFERENCE
CHEST, 69: 2, FEBRUARY, 1976 SUPPLEMENT
•
'£
.••.
. ••-
1 Banaszak EF, Thiede WH, Fink JN: Hypersensitivity pneumonitis due to contaminated air conditioner. N Eng! J Med 283:271-276, 1970 2 Banaszak EF, Barboriak J, Fink J, et al: Epidemiological studies relating thermophilic fungi and hypersensitivity lung syndromes. Am Rev Resp Dis 110:585-591, 1974 FIGURE 1. Diffuse bilateral interstitial changes seen at both bases, slightly more prominent on the left in case 1 at time of diagnosis.
Desquamative Interstitial Pneumonia following Chronic Nitrofurantoin Therapy*
filtrates, more prominent in the bases (Fig 1). Pulmonary function studies were characterized by a restrictive defect and moderate impairment of gas transfer (Table 1). Lung biopsies examined by light microscopy in two patients were characterized by large numbers of intraalveolar mononuclear cells and other pathologic changes consistent with desquamative interstitial pneumonia (DIP), 9 in contrast to the nonspecific fibrosing interstitial pneumonitis previously reported by others (Fig 2) . The appearance of one biopsy studied by electron microscopy was similar to that described for DIP. Hyperplastic cells lining alveolar septa had microvilli and contained lamellar inclusions typical of granular (type II) pneumocytes; intra-alveolar cells had the morphologic features of macrophages (Fig 3) , including long pseudopodia, numerous electron-dense cytoplasmic granules, and only rarely a lamellar inclusion. Immunofluorescence studies on one biopsy showed deposits of IgE and C3 component of complement within interstitial cells. By in vitro studies, nitrofurantoin failed to induce lymphoblast transformation or release of
Roger C. Bone, M.D.;•• John Wolfe, M.D.;t Richard E. Sobonya, M.D.** Gerald R. Kerby, M.D.;t Daniel Stechschulte, M.D.;t William E. Ruth, M.D.;§ and Maura Welchjj
hirteen cases of pulmonary fibrosis attributed to T chronic nitrofurantoin use have been described previously .1-8 Three additional patients who developed diffuse interstitial lung disease during chronic (two to five years) nitrofurantoin therapy have been studied. Clinical findings included exertional dyspnea and basilar rales. Chest roentgenograms demonstrated interstitial in*From the Departments of Internal Medicine, Pathology and Oncology, University of Kansas Medical Center, Kansas City, Kansas. Supported in part by NIH Training grants 173701, 5-T01B-M01783, and Hospital Research grant 712227. 0 0 Assistant Professor. tPulmonary Fellow. tAssociate Professor. §Professor. [!Medical Student.
Table I -Selected PulmoiUJry Function Before and After Treatment of Nitrofurantoin LuRfi Di.ea•e*
Patient No. 1 Before After
Measurement
Patient No. 2 Before After
Patient No. 3 Before After
Forced Vital Capacity, Liter
1.70 (67%)
2.00 (79%)
3.00 (65%)
4.55 (99%)
2.36 (59%)
4.16 (106%)
Total Lung Capacity, Liter
3.67 (100%)
3.50 (96%)
4.79 (80%)
6.15 (103%)
4.58 (79%)
6.30 (108%)
DLCo, t ml/min/mm Hg
12 (70%)
11.4 (67%)
16.5 (65%)
18.2 (72%)
11.3 (61%)
18.2 (98%)
Pa01, mm Hg
76
82
66
83
80
70t
83
84t
PaCO,, mm Hg
34
41
36
34
38
44i
34
42t
pH, units
7.43
7.34
7.44
7.52
7.38
7.52
*Patient No. 1 treated by discontinuing nitrofurantoin. Patients No. 2 and No. 3 treated by discontinuing nitrofurantoin and beginning corticosteroids tSingle breath diffusion tExercise blood gas values Parentheses = percent predicted value
296
18TH ASPEN CONFERENCE
CHEST, 69: 2, FEBRUARY, 1976 SUPPLEMENT
•
'£
.••.
. ••-
