Case Report from the Thoracic Services Boston University Medical School Respiration 32: 81-92 (1975)
Silo-Filler’s Disease1 W illiam L. M orrissey, I ra A. G ould , Charles B. C arrington and E dward A. G aensler Departments of Medicine and Surgery, School of Medicine, Boston University, Boston, Mass., and the Department of Pathology, School of Medicine, Yale University New Haven, Conn. Abstract. The effects of oxides of nitrogen Key Words inhalation are reported in a 21-year-old gar Oxides of nitrogen dener exposed to silage gas. Initial nausea, Silo-filler's disease cough and fever remitted, but respiratory fail Nitrogen dioxide ure developed 3 weeks later. Roentgenograms Silage gas and lung function studies revealed pulmonary Respiratory distress in the adult edema, volume restriction, and severely im Stiff lung paired gas exchange. Needle biopsy showed a Chemical pneumonitis nonspecific interstitial pneumonia. With ster oid therapy all functional parameters except diffusing capacity returned to normal. Failure to inquire about non-occupational activities led to delayed diagnosis. A brief review of toxic effects of nitrogen oxides is presented.
Introduction
A large spectrum of disorders is associated with acute interstitial pneu monia and lung edema, or what has been referred to as ‘stiff lung’, ‘re spiratory distress in the adult’ or ‘congestive atelectasis’. A patient is pre sented who developed respiratory symptoms after exposure to nitrogen oxides in a silo. Failure to inquire concerning recreational activities not associated with his regular work delayed the diagnosis.
Received: February 1, 1974; accepted: February 7, 1974.
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
' This study was supported in part by a Pulmonary SCOR grant (HL-15063), a Research grant (HL-05933), a Training grant (HL-5562), and a Career Award (HI.-1173), all from the National Heart and Lung Institute, US Public Health Service.
82
M orrtssey/G ould /C arrington/G aensler
Fig.l. A needle biopsy of the lung (a) shows a nonspecific interstitial infiltrate with focal epithelial metaplasia, organization and some fibrosis. HE. X 96. At higher magnification (b) the infiltration is seen to consist of monocytes, lympho cytes and abundant vacuolated macrophages in the airspaces. HE. X 240.
J. G., a 21-year-old mason and landscaper, was in excellent health until Decem ber, 1971, when, helping his brother on a farm, lie entered a silo which had been filled with corn some weeks earlier. He noticed a ‘brown steam’ rising from the sil-
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Case Report
83
age and left after 20 min because of irritation from the fumes. During the following month he re-entered the silo 3 times without difficulty. However, 1 h after entering the silo for the fourth time on January 19, 1972, he noted the abrupt onset of nau sea, vomiting, chills and fever. Soon he was bothered by a severe cough productive of greenish sputum, and when he sought medical attention 9 days later, antibiotics and expectorants were prescribed. His fever subsided but cough and nausea persist ed. After medication was discontinued 2 weeks later, fever, severe shortness of breath, and pleuritic chest pain required hospitalization. On admission, February 13, he was in respiratory distress with tachycardia and rales. The initial chest roentgenogram showed only faint outlines of the lungs
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Silo-Filler’s Disease
84
M orrissey/G ogld /C arrington/G aensler
which were almost completely obscured by a dense, homogenous ‘ground glass’ pat tern. Breathing room air, the arterial Po2 was 46 Torr, the Pco2 31 Torr, and the pH 7.47. The peripheral white blood cell count was 21,000 with 75% polymorpho nuclear leukocytes and 1% eosinophils. Hematocrit, LE cell preparation, RA latex fixation, urinalysis, and electrocardiogram were unremarkable. Blood, sputum and throat cultures yielded no significant pathogens. The history of exposure to sil age gas was not obtained, and a diagnosis of bilateral bronchopneumonia was made. Carbencillin and gentamicin for 5 days failed to cause improvement. He was transferred to a University hospital on February 19 in severe respiratory failure with profuse diaphoresis, weakness, and fever. Examination revealed coarse ‘scratchy’ breath sounds throughout both lung fields, bilateral inspiratory rales, and a third heart sound. The chest film showed little change. The arterial Po2 was 25 Torr, Pco2 32 Torr, and pH 7.50. The white cell count was 27,000 with 96% po lymorphonuclear leukocytes. Other than hypoalbuminemia (albumin 2.6 g, globulin 3.3 g) and elevated hepatic enzymes with l.DH 400. SGOT 700 and SGPT940, labo ratory studies, including BUN, creatinine, urinalysis, cold and heterophile agglutin ins, and sputum examination for bacteria and fungi were unremarkable.
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Fig. 2. A chest roentgenogram 8 days after hospital admission and 1 month after last exposure in the silo showed both lungs obliterated by infiltrates, suggesting massive pulmonary edema.
Silo-Filler’s Disease
85
Therapy initially consisted of intermittent positive pressure breathing, oxygen, chloramphenicol and erythromycin. Differential diagnoses included the large spec trum of ‘respiratory distress in the adult’, and therefore a needle biopsy was per formed. Histologically, there was a nonspecific reaction consisting of an interstitial infiltrate of monocytes and lymphocytes, abundant vacuolated macrophages in the airspaces, focal epithelial metaplasia, and focal organization with fibrosis (fig. la, b). The reaction was consistent with an ‘obstructive pneumonia’ sometimes seen distal to bronchiolitis obliterans. The chest film at this time still showed dense bilat eral infiltration with an ‘alveolar pattern’ suggestive of pulmonary edema (fig. 2). Following biopsy, and now with a history of silo exposure, antibiotics were dis continued, and 100 mg of hydrocortisone was given intravenously every 6 h. Within 24 h there was improvement; after 48 h vital signs had returned to normal, cough and sputum had diminished, arterial blood was better oxygenated, and the leukocyte count had decreased slightly; and after 72 h the chest roentgenogram showed clear ing of edema with an ‘interstitial’ infiltrate now clearly visible (fig. 3). As he im proved. oxygen and steroids were gradually discontinued. On March 4 the appear-
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Fig. 3. Three days following initiation of corticosteroid therapy, there was some clearing of edema with an ‘interstitial’ infiltrate uniformly disseminated and extend ing to the lung periphery.
86
M orrissey/G ould /C arrington;G aensler
ance of the chest film was much improved with still an uniform reticular and lin ear pattern (fig. 4). On March 6, 1972, 46 days after his exposure, arterial Poa was 86 Torr, Pcoa 24Torr, and pH 7.42. The white blood cell count had decreased to 14,000, and the roentgenogram had cleared. Pulmonary function tests, now possible for the first time, showed marked restriction of lung volumes without evidence of obstruction. The reduced single breath diffusing capacity and widened alveolar-arterial Oa dif ference confirmed persisting impairment of gas exchange (table 1). After 2 weeks without medication, a productive cough returned and the chest roentgenogram showed reappearance of some linear shadows particularly radiating from the left hilus (fig. 5). Prednisone, 20 mg daily, was reinstituted. Three months later he had facial and truncal acne and had gained 5 lb., but physical examination and the chest film were now normal. Pulmonary function studies revealed improve ment in lung volumes and gas exchange, with only the single breath diffusing capac ity remaining abnormal (table I).
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Fig. 4. Shortly before discharge there was still a uniform reticular and linear pattern with a ground-glass appearance, but the patchy densities had largely disap peared. Within a few days the roentgenogram appeared normal.
Silo-Filler's Disease
87
Fig. 5. Corticosteroids were discontinued. Two weeks later symptoms reap peared, and the chest roentgenogram at this time showed renewed reticular infiltra tion, particularly radiating from the left hilus. He continued taking prednisone and was examined again in November, 1972, 8 months after discharge. He was asymptomatic, but had gained 50 lb. and had devel oped severe acne, ‘moon facies’, and multiple large red striae. A slightly reduced single breath diffusing capacity persisted (table I). Steroids were gradually discontinued, and in April, 1973, 16 months after his ex posure, he had less striae and acne, although he was still overweight. Physical exam ination was otherwise normal as was his chest roentgenogram (fig. 6). Pulmonary function tests continued to show improvement in lung volume, but the single breath diffusing capacity remained reduced (table I).
The first silo was built in the United States in 1875 [19], but unex plained deaths occurring in these structures were not reported until 1914
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Discussion
88
M orrissf.y/G ould /C arrington 'G aenslkr
[7]. For some time these accidents were attributed to asphyxia from high levels of carbon dioxide, but in 1949 the offending agent was identified as a mixture of oxides of nitrogen, especially NO. N 0 2, and N20 4 [16]. The term ‘silo-filler’s disease’ was first used in 1956 when milder forms of the disease were described [4, 6,11]. The toxic effects of nitrogen oxides had been well established in other industries. Release of nitrogen oxides with injury to workers has been re ported with electroplating, acetylene welding, combustion of cellulose film [15] and plastics, detonation of explosives, numerous industrial reac tions involving nitric acid [3, 12], and unusual exposures such as burning of shoe polish. The clinical results of exposure were similar in all of these situations, which differed only in the mode of gas generation. In silos the nitrogen oxides are produced by fermentation of ripe sil age, usually corn or alfalfa, which contain nitrates that react with enzymes to form nitrites and oxygen. The nitrites combine with organic acids
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Fig. 6. The roentgenogram about 1 year following the acute illness was normal.
Table 1
March 6, 1972
March 20, May 10, 1972 1972
November 28, 1972
April 25, Predicted 1973
194 4.7 4.0 86 5.0 3.8
199 4.9 4.2 87 5.4 3.3 1.6 1.1 6.1 19
186 5.1 4.3 84 5.4
Rest
1. Mechanics and tang volumes 172 4.4 4.2 97 6.0 3.4 1.3 0.9 5.6 17
-
3.1 3.0 95 5.4 1.8 1.3 0.8 3.9 20
1 .0
1.5 1.3 3.8 34
1 .1
1.2 6.1 20
Rest
Rest
Rest
Ex.
Rest
Ex.
Rest
64
83 -
-
-
98 86 12 7.56 40 308 6.2 2.0 0.73 21 64 26 7
104 78 26 7.44 41 1,328 31.3 2.4 0.88 25 37
109 91 18 7.42 34 303 6.6 2.2 0.78 13 62 28 6
117 85 32 7.40 33 1,774 50.6 2.9
88
-
-
1.3 6.4 20 Ex.
II. Steady state rest and exercise ( Ex.) Alveolar Oa tension (Pao2), Torr Arterial O2 tension (Pao,), Torr P a o s —Pao2, Torr Arterial pH Arterial CO2 tension (Pac02 >, Torr Oxygen uptake (Vo2), ml STPD/min Ventilation ( V e ), 1 BTPS/min Vent, equiv. (Ve/0 2), 1/100 ml 0 2 Respiratory exchange ratio (R) DifT. cap., steady state (D lcoSS), ml/min/Torr Fraction CO removed (Fco), % DifT. cap., single br. ( D l c o SB), ml/min/Torr Right to left shunt, % of CO
7.44 29
7.45 43
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1 .0 1
25 30 —
-
-
7.46 36
105 >90 90 40 37 ±3
Silo-Filler’s Disease1 W illiam L. M orrissey, I ra A. G ould , Charles B. C arrington and E dward A. G aensler Departments of Medicine and Surgery, School of Medicine, Boston University, Boston, Mass., and the Department of Pathology, School of Medicine, Yale University New Haven, Conn. Abstract. The effects of oxides of nitrogen Key Words inhalation are reported in a 21-year-old gar Oxides of nitrogen dener exposed to silage gas. Initial nausea, Silo-filler's disease cough and fever remitted, but respiratory fail Nitrogen dioxide ure developed 3 weeks later. Roentgenograms Silage gas and lung function studies revealed pulmonary Respiratory distress in the adult edema, volume restriction, and severely im Stiff lung paired gas exchange. Needle biopsy showed a Chemical pneumonitis nonspecific interstitial pneumonia. With ster oid therapy all functional parameters except diffusing capacity returned to normal. Failure to inquire about non-occupational activities led to delayed diagnosis. A brief review of toxic effects of nitrogen oxides is presented.
Introduction
A large spectrum of disorders is associated with acute interstitial pneu monia and lung edema, or what has been referred to as ‘stiff lung’, ‘re spiratory distress in the adult’ or ‘congestive atelectasis’. A patient is pre sented who developed respiratory symptoms after exposure to nitrogen oxides in a silo. Failure to inquire concerning recreational activities not associated with his regular work delayed the diagnosis.
Received: February 1, 1974; accepted: February 7, 1974.
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
' This study was supported in part by a Pulmonary SCOR grant (HL-15063), a Research grant (HL-05933), a Training grant (HL-5562), and a Career Award (HI.-1173), all from the National Heart and Lung Institute, US Public Health Service.
82
M orrtssey/G ould /C arrington/G aensler
Fig.l. A needle biopsy of the lung (a) shows a nonspecific interstitial infiltrate with focal epithelial metaplasia, organization and some fibrosis. HE. X 96. At higher magnification (b) the infiltration is seen to consist of monocytes, lympho cytes and abundant vacuolated macrophages in the airspaces. HE. X 240.
J. G., a 21-year-old mason and landscaper, was in excellent health until Decem ber, 1971, when, helping his brother on a farm, lie entered a silo which had been filled with corn some weeks earlier. He noticed a ‘brown steam’ rising from the sil-
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Case Report
83
age and left after 20 min because of irritation from the fumes. During the following month he re-entered the silo 3 times without difficulty. However, 1 h after entering the silo for the fourth time on January 19, 1972, he noted the abrupt onset of nau sea, vomiting, chills and fever. Soon he was bothered by a severe cough productive of greenish sputum, and when he sought medical attention 9 days later, antibiotics and expectorants were prescribed. His fever subsided but cough and nausea persist ed. After medication was discontinued 2 weeks later, fever, severe shortness of breath, and pleuritic chest pain required hospitalization. On admission, February 13, he was in respiratory distress with tachycardia and rales. The initial chest roentgenogram showed only faint outlines of the lungs
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Silo-Filler’s Disease
84
M orrissey/G ogld /C arrington/G aensler
which were almost completely obscured by a dense, homogenous ‘ground glass’ pat tern. Breathing room air, the arterial Po2 was 46 Torr, the Pco2 31 Torr, and the pH 7.47. The peripheral white blood cell count was 21,000 with 75% polymorpho nuclear leukocytes and 1% eosinophils. Hematocrit, LE cell preparation, RA latex fixation, urinalysis, and electrocardiogram were unremarkable. Blood, sputum and throat cultures yielded no significant pathogens. The history of exposure to sil age gas was not obtained, and a diagnosis of bilateral bronchopneumonia was made. Carbencillin and gentamicin for 5 days failed to cause improvement. He was transferred to a University hospital on February 19 in severe respiratory failure with profuse diaphoresis, weakness, and fever. Examination revealed coarse ‘scratchy’ breath sounds throughout both lung fields, bilateral inspiratory rales, and a third heart sound. The chest film showed little change. The arterial Po2 was 25 Torr, Pco2 32 Torr, and pH 7.50. The white cell count was 27,000 with 96% po lymorphonuclear leukocytes. Other than hypoalbuminemia (albumin 2.6 g, globulin 3.3 g) and elevated hepatic enzymes with l.DH 400. SGOT 700 and SGPT940, labo ratory studies, including BUN, creatinine, urinalysis, cold and heterophile agglutin ins, and sputum examination for bacteria and fungi were unremarkable.
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Fig. 2. A chest roentgenogram 8 days after hospital admission and 1 month after last exposure in the silo showed both lungs obliterated by infiltrates, suggesting massive pulmonary edema.
Silo-Filler’s Disease
85
Therapy initially consisted of intermittent positive pressure breathing, oxygen, chloramphenicol and erythromycin. Differential diagnoses included the large spec trum of ‘respiratory distress in the adult’, and therefore a needle biopsy was per formed. Histologically, there was a nonspecific reaction consisting of an interstitial infiltrate of monocytes and lymphocytes, abundant vacuolated macrophages in the airspaces, focal epithelial metaplasia, and focal organization with fibrosis (fig. la, b). The reaction was consistent with an ‘obstructive pneumonia’ sometimes seen distal to bronchiolitis obliterans. The chest film at this time still showed dense bilat eral infiltration with an ‘alveolar pattern’ suggestive of pulmonary edema (fig. 2). Following biopsy, and now with a history of silo exposure, antibiotics were dis continued, and 100 mg of hydrocortisone was given intravenously every 6 h. Within 24 h there was improvement; after 48 h vital signs had returned to normal, cough and sputum had diminished, arterial blood was better oxygenated, and the leukocyte count had decreased slightly; and after 72 h the chest roentgenogram showed clear ing of edema with an ‘interstitial’ infiltrate now clearly visible (fig. 3). As he im proved. oxygen and steroids were gradually discontinued. On March 4 the appear-
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Fig. 3. Three days following initiation of corticosteroid therapy, there was some clearing of edema with an ‘interstitial’ infiltrate uniformly disseminated and extend ing to the lung periphery.
86
M orrissey/G ould /C arrington;G aensler
ance of the chest film was much improved with still an uniform reticular and lin ear pattern (fig. 4). On March 6, 1972, 46 days after his exposure, arterial Poa was 86 Torr, Pcoa 24Torr, and pH 7.42. The white blood cell count had decreased to 14,000, and the roentgenogram had cleared. Pulmonary function tests, now possible for the first time, showed marked restriction of lung volumes without evidence of obstruction. The reduced single breath diffusing capacity and widened alveolar-arterial Oa dif ference confirmed persisting impairment of gas exchange (table 1). After 2 weeks without medication, a productive cough returned and the chest roentgenogram showed reappearance of some linear shadows particularly radiating from the left hilus (fig. 5). Prednisone, 20 mg daily, was reinstituted. Three months later he had facial and truncal acne and had gained 5 lb., but physical examination and the chest film were now normal. Pulmonary function studies revealed improve ment in lung volumes and gas exchange, with only the single breath diffusing capac ity remaining abnormal (table I).
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Fig. 4. Shortly before discharge there was still a uniform reticular and linear pattern with a ground-glass appearance, but the patchy densities had largely disap peared. Within a few days the roentgenogram appeared normal.
Silo-Filler's Disease
87
Fig. 5. Corticosteroids were discontinued. Two weeks later symptoms reap peared, and the chest roentgenogram at this time showed renewed reticular infiltra tion, particularly radiating from the left hilus. He continued taking prednisone and was examined again in November, 1972, 8 months after discharge. He was asymptomatic, but had gained 50 lb. and had devel oped severe acne, ‘moon facies’, and multiple large red striae. A slightly reduced single breath diffusing capacity persisted (table I). Steroids were gradually discontinued, and in April, 1973, 16 months after his ex posure, he had less striae and acne, although he was still overweight. Physical exam ination was otherwise normal as was his chest roentgenogram (fig. 6). Pulmonary function tests continued to show improvement in lung volume, but the single breath diffusing capacity remained reduced (table I).
The first silo was built in the United States in 1875 [19], but unex plained deaths occurring in these structures were not reported until 1914
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Discussion
88
M orrissf.y/G ould /C arrington 'G aenslkr
[7]. For some time these accidents were attributed to asphyxia from high levels of carbon dioxide, but in 1949 the offending agent was identified as a mixture of oxides of nitrogen, especially NO. N 0 2, and N20 4 [16]. The term ‘silo-filler’s disease’ was first used in 1956 when milder forms of the disease were described [4, 6,11]. The toxic effects of nitrogen oxides had been well established in other industries. Release of nitrogen oxides with injury to workers has been re ported with electroplating, acetylene welding, combustion of cellulose film [15] and plastics, detonation of explosives, numerous industrial reac tions involving nitric acid [3, 12], and unusual exposures such as burning of shoe polish. The clinical results of exposure were similar in all of these situations, which differed only in the mode of gas generation. In silos the nitrogen oxides are produced by fermentation of ripe sil age, usually corn or alfalfa, which contain nitrates that react with enzymes to form nitrites and oxygen. The nitrites combine with organic acids
Downloaded by: Stockholm University Library 130.237.165.40 - 12/8/2018 11:11:42 AM
Fig. 6. The roentgenogram about 1 year following the acute illness was normal.
Table 1
March 6, 1972
March 20, May 10, 1972 1972
November 28, 1972
April 25, Predicted 1973
194 4.7 4.0 86 5.0 3.8
199 4.9 4.2 87 5.4 3.3 1.6 1.1 6.1 19
186 5.1 4.3 84 5.4
Rest
1. Mechanics and tang volumes 172 4.4 4.2 97 6.0 3.4 1.3 0.9 5.6 17
-
3.1 3.0 95 5.4 1.8 1.3 0.8 3.9 20
1 .0
1.5 1.3 3.8 34
1 .1
1.2 6.1 20
Rest
Rest
Rest
Ex.
Rest
Ex.
Rest
64
83 -
-
-
98 86 12 7.56 40 308 6.2 2.0 0.73 21 64 26 7
104 78 26 7.44 41 1,328 31.3 2.4 0.88 25 37
109 91 18 7.42 34 303 6.6 2.2 0.78 13 62 28 6
117 85 32 7.40 33 1,774 50.6 2.9
88
-
-
1.3 6.4 20 Ex.
II. Steady state rest and exercise ( Ex.) Alveolar Oa tension (Pao2), Torr Arterial O2 tension (Pao,), Torr P a o s —Pao2, Torr Arterial pH Arterial CO2 tension (Pac02 >, Torr Oxygen uptake (Vo2), ml STPD/min Ventilation ( V e ), 1 BTPS/min Vent, equiv. (Ve/0 2), 1/100 ml 0 2 Respiratory exchange ratio (R) DifT. cap., steady state (D lcoSS), ml/min/Torr Fraction CO removed (Fco), % DifT. cap., single br. ( D l c o SB), ml/min/Torr Right to left shunt, % of CO
7.44 29
7.45 43
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1 .0 1
25 30 —
-
-
7.46 36
105 >90 90 40 37 ±3
