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60-Year-Old Man With Respiratory Distress and Confusion

      A 60-year-old farmer from southeastern Minnesota was brought to the emergency department by paramedics. The patient was conscious, but severe dyspnea prevented elicitation of an extended medical history. He was also noted to be recently separated from his wife of many years. His old medical records revealed no major past medical problems. He had never used tobacco and had no risk factors for human immunodeficiency virus (HIV) infection. Before the current illness, he had been working long hours for the fall harvest. His farm supervisor stated that the patient had left work early that day, and he had been missing for several hours. The supervisor had searched for the patient and found him alone in his truck next to a barn, confused and breathless. An ambulance had been summoned.
      On physical examination, the patient had a blood pressure of 90/72 mm Hg, pulse rate of 110 beats/min, respiratory rate of 40/min, and temperature of 37.0°C. He appeared to be in severe respiratory distress and was confused. His pupils were of normal size and equally reactive to light. He had bilateral conjunctivitis and dry oral mucosa. Examination of the lungs disclosed diffuse bilateral inspiratory crackles. Cardiac examination revealed regular tachycardia without a murmur or gallop rhythm. The jugular venous pressure was not increased. The abdomen was normal. His extremities were cool with palpable pulses. Cyanosis was present, and clubbing was absent. No focal neurologic deficits were noted. Arterial blood gas analysis, while he breathed room air, revealed an oxygen tension of 32 mm Hg, a carbon dioxide tension of 32 mm Hg, a pH of 7.30, a methemoglobin of 1%, and a carboxyhemoglobin level of less than 1%. Blood tests showed a leukocyte count of 32.7 × 109/L with a shift to the left, a hemoglobin level of 16.1 g/dL, and a hematocrit of 48.1%. An electrocardiogram disclosed a sinus tachycardia. A chest roentgenogram revealed bilateral dense alveolar infiltrates (Fig. 1).
      Figure thumbnail gr1
      Fig. 1Chest roentgenogram at time of admission, showing bilateral diffuse alveolar infiltrates.
      • 1.
        Which one of the following is the least likely to have caused this patient's respiratory failure?
        • a.
          Hypersensitivity pneumonitis
        • b.
          Pulmonary mycotoxicosis (organic dust toxic syndrome)
        • c.
          Paraquat poisoning
        • d.
          Carbon monoxide poisoning
        • e.
          Legionella infection
      Hypersensitivity pneumonitis, pulmonary mycotoxicosis, and paraquat poisoning are usually encountered in farmers or others who are frequently exposed to the responsible etiologic agents. All three conditions are known to cause acute and rapidly progressive respiratory failure. Therefore, they should be considered in this patient, although the chest roentgenographic features appear severe for the diagnosis of hypersensitivity pneumonitis. Hypersensitivity pneumonitis is an occupational lung disorder of farmworkers commonly called “farmer's lung.” It is an immune-mediated, infiltrative lung disease that arises from sensitization and recurrent exposures to antigens. Among farmers, thermophilic actinomycetes from moldy composts are frequently implicated. Hypersensitivity pneumonitis, when it is insidious in onset and recurs, can cause irreversible and chronically disabling sequelae without early treatment. The diagnostic criteria for this entity include a history of exposure to an antigen, such as could occur with farming, followed by respiratory difficulties. Distress can occur suddenly, as in this patient. In an acute case, influenza-like symptoms develop 4 to 6 hours after exposure. A chest roentgenogram usually demonstrates nodular or diffuse lung infiltrates, consistent with the findings in this patient.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Gurney JW
      • Unger JM
      • Dobry CA
      • Mitby JK
      • Von Essen SG
      Agricultural disorders of the lung.
      • Kokkarinen Jl
      • Tukiainen HO
      • Terho EO
      Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung.
      • Kokkarinen Jl
      • Tukiainen HO
      • Terho EO
      Recovery of pulmonary function in farmer's lung: a five-year follow-up study.
      Pulmonary mycotoxicosis clinically resembles hypersensitivity pneumonitis, but it is a nonallergic, noninfectious respiratory illness caused by inhalation of a massive concentration of organic dust from moldy silage, hay, or grain. Affected persons can experience a syndrome of fever, chills, dyspnea, and myalgias approximately 4 to 6 hours after exposure to contaminated dusts. Pulmonary mycotoxicosis may be associated with other signs seen in this patient, such as leukocytosis and lung crackles on physical examination. Chest roentgenographic findings are described as being normal to diffuse fine reticulonodular infiltrates. Because it is a toxic rather than an allergic phenomenon, prior sensitization is not a requirement.
      • Gurney JW
      • Unger JM
      • Dobry CA
      • Mitby JK
      • Von Essen SG
      Agricultural disorders of the lung.
      • Emanuel DA
      • Wenzel FJ
      • Lawton BR
      Pulmonary mycotoxicosis.
      • May H
      • Stallones L
      • Darrow D
      • Pratt DS
      Organic dust toxicity (pulmonary mycotoxicosis) associated with silo unloading.
      Paraquat is an agricultural herbicide known to cause dose-related pulmonary damage. Large doses are needed to produce pulmonary edema, whereas smaller repeated doses will cause the subclinical lung changes of pulmonary fibrosis. Toxic exposures are usually due to dermal absorption, although inhalational exposures can occur.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Gurney JW
      • Unger JM
      • Dobry CA
      • Mitby JK
      • Von Essen SG
      Agricultural disorders of the lung.
      In this patient, carbon monoxide poisoning was initially suggested by the history (a confused patient with dyspnea, found alone in a vehicle, after recent marital stress) but ultimately considered unlikely because of the blood gas findings of a normal carboxyhemoglobin level and hypoxemia and the abnormal chest roentgenographic features. Although the roentgenographic abnormalities appeared severe, infections with Legionella, Mycoplasma, or a severe community-acquired bacterial pneumonia should also be considered, in light of the increased leukocyte count and a compatible chest roentgenogram in this patient.
      This patient required tracheal intubation, mechanical ventilation, and monitoring in the intensive-care unit. He received a high fractional concentration of inspired oxygen and positive end-expiratory pressure to maintain an adequate blood oxygen saturation. His blood pressure normalized after initial fluid resuscitation with 4.5 L of crystalloid solution. He was then stable, alert, and oriented; further diagnostic studies were considered.
      • 2.
        At this point, which one of the following diagnostic tests is inappropriate?
        • a.
          Bronchoalveolar lavage for cultures and acid-fast bacilli
        • b.
          Serologie tests for identification of possible exposures to Aspergillus, Candida, Histoplasma, Coccidioides, Blastomyces, and Cryptococcus
        • c.
          Serologie tests for identification of possible exposures to Micropolyspora and Thermoactinomyces
        • d.
          Pulmonary function tests
        • e.
          Alcohol and drug screens
      Bronchoscopically performed bronchoalveolar lavage is both a relatively safe and a sensitive means of diagnosing an infectious cause such as fungal, mycobacterial, bacterial, and Legionella infections. Because hypersensitivity pneumonitis and fungal infections (with infectious or immunologic reactions) are part of the differential diagnosis in this patient, serologic testing to detect the common etiologic agents responsible for mycoses and hypersensitivity pneumonitis is reasonable. If this patient's acute illness is the result of a first exposure to antigens or fungal organisms, however, serologic results may be negative during the initial phase of the illness. Although positive results on allergic panels and fungal serology are not diagnostic of allergic lung conditions or hypersensitivity pneumonitis, they corroborate the clinical irnpression.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Kokkarinen Jl
      • Tukiainen HO
      • Terho EO
      Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung.
      • Emanuel DA
      • Wenzel FJ
      • Lawton BR
      Pulmonary mycotoxicosis.
      Pulmonary function tests (lung volumes, expiratory flows, and diffusion capacity) would add little to the initial diagnosis in this patient, and they are not indicated in the presence of acute respiratory failure. Moreover, they should not be performed on an intubated patient, except in a research setting. Although pulmonary function tests do not have a diagnostic role in this acute illness, they may be useful for monitoring the functional impairment of this patient during the subsequent months. Because drug and alcohol screening could disclose any abuse that may complicate the patient's clinical picture, such studies should be considered in this patient.
      Before the performance of further tests, the patient was able to provide additional details of his medical history. The day before his admission, the patient had filled a concrete “top-unloading” silo with freshly chopped corn. He did not recall being exposed to dust. That evening he experienced mild shortness of breath and dyspnea on exertion. The next morning he climbed an enclosed access chute to the top of the silo. After spreading the freshly cut silage at the top of the silo for approximately 20 minutes, he descended through the access chute. During his descent, he noticed a “chlorinelike” odor. Shortly thereafter, he began to feel a tightness in his chest. He had to quit work at noon because of progressive shortness of breath and irritation of his eyes. His respiratory distress worsened in the evening. Even though he managed to get to his truck, he was unable to drive his vehicle for help.
      • 3.
        On the basis of the new historical information, which one of the following is most likely to have caused this patient's pulmonary disease?
        • a.
          Chemical injury from inhalation of oxides of nitrogen (silo filler's disease)
        • b.
          Dermal absorption of chemicals from the silage
        • c.
          Chemical injury from hypersensitivity to organic proteins
        • d.
          Pulmonary embolism
        • e.
          Infection with thermophilic fungal spores
      The patient's history and manifestations now strongly suggest silo filler's disease. This agricultural lung disease is attributable to the acute inhalation of gaseous oxides of nitrogen produced by bacteria in freshly cut silage. The chlorine odor noted by the patient is typical. The mechanism of injury is direct chemical toxicity to the lung. Dermal Dermal absorption is not a major factor in silo filler's disease (although it may be in other organic pneumoconioses). The patient's occupation places him at risk for hypersensitivity pneumonitis; however, this lung injury is caused by hypersensitivity to organic proteins, rather than a direct chemical injury to the lung. Hypersensitivity pneumonitis is a cellular immune process that is not mediated by antibodies but may be associated with circulating IgG antibodies.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Kokkarinen Jl
      • Tukiainen HO
      • Terho EO
      Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung.
      • Emanuel DA
      • Wenzel FJ
      • Lawton BR
      Pulmonary mycotoxicosis.
      Even though pulmonary embolism is always a consideration ir? acute respiratory distress, it is highly unlikely because of the clinical features in this patient. In addition, he had been extremely active during the hours preceding the acute dyspnea and had no history of or risk factors for hypercoagulability. Inhalation of dust containing thermophilic fungal spores can cause lung injury by an immune-mediated rather than an infectious process. The patient did not recall exposure to any dusts or molds while working in the silo. Such a negative history, however, may be misleading because many subjects exposed to smaller amounts of offending antigens may not recognize or recollect the exposure.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Emanuel DA
      • Wenzel FJ
      • Lawton BR
      Pulmonary mycotoxicosis.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      Nonetheless, the details of the exposure, the clinical features, and the severity of this patient's respiratory distress all suggested the diagnosis of silo filler's disease.
      The patient was initially treated with high-dose corticosteroids and successfully weaned from mechanical ventilation in 2 days. A follow-up chest roentgenogram showed considerable improvement on the 10th day of his illness.
      • 4.
        In light of the clinical diagnosis, which one of the following measures is most likely to help prevent similar episodes?
        • a.
          Education of agricultural workers at risk
        • b.
          Inspection of the ventilation systems in silos
        • c.
          Wearing of a face mask and gloves in the workplace
        • d.
          Use of oxygen-monitoring devices in silos
        • e.
          Screening of fellow employees with chest roentgenography, pulmonary function tests, and skin sensitivity tests
      The key element in the prevention of silo filler's disease is the education of farmers and other agricultural workers at risk to avoid exposure and to recognize the signs of silo gas. Additionally, farmers should be aware of the locations where gas is likely to accumulate, and they should be alert for the early symptoms of exposure. In the current case, the patient had used a silo ventilation system for 20 minutes before entering a silo when high concentrations of gas were likely-less than 48 hours after filling. This action was contrary to the general recommendation to avoid entry into freshly filled silos for 14 days. Moreover, when entry into a recently filled silo is absolutely necessary, the recommendations are to inspect for signs of gas, open doors, and ventilate with mechanical blowers for at least 1 hour before entry and during work in the silo.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      Mechanical failures of silo ventilation systems are often implicated in silo filler's disease, although this finding is not universal. Although Although inspections of the ventilation systems in silos might be a reasonable adjunct to the education of farmers, an effective blower alone provides only secondary protection. Oxides of nitrogen are heavier than air, tend to accumulate in poorly ventilated areas of silos, and are difficult to displace.
      • Zwemer Jr, FL
      • Pratt DS
      • May Il
      Silo filler's disease in New York State.
      Therefore, functional blowers can only supplement the education of farmers about their proper use, the dangers of climbing into recently filled silos, and the signs of gas in silage. Face masks and gloves would not provide adequate protection against a toxin with a small molecular structure, such as oxides of nitrogen. When exposure to this toxin is unavoidable, specialized protective and respiratory ventilation equipment is needed. Monitoring oxygen concentrations in agricultural structures would not provide adequate protection, inasmuch as concentrations of oxides of nitrogen as small as 50 to 500 parts per million can be toxic, even in the presence of an adequate fraction of oxygen.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      Of importance, however, low concentrations of oxygen in silos may exacerbate the severity of exposures.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      No current guidelines indicate the need to screen farmworkers for silo filler's disease, although many more workers than simply those who seek medical care are probably affected with less severe cases of this disease.
      • Zwemer Jr, FL
      • Pratt DS
      • May Il
      Silo filler's disease in New York State.
      After receiving education about workplace precautions, the patient was dismissed with a prescription for prednisone, 60 mg orally once a day for 3 weeks. During an additional period of 7 weeks, the prednisone dosage was tapered and then discontinued. His dyspnea at rest resolved, and further evaluations revealed improvement in his resting arterial oxygen tension.
      • 5.
        On the basis of the clinical diagnosis, which one of the following complications is more likely to occur than the others in this patient?
        • a.
          Lymphocytic interstitial pneumonitis
        • b.
          Pulmonary fibrosis
        • c.
          A chronic systemic autoimmune disease
        • d.
          Recurrence of symptoms without further exposure to the offending agent
        • e.
          Bronchiolitis obliterans
      The acute mortality associated with silo filler's disease in larger case series is estimated between 9 and 20%.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      • Zwemer Jr, FL
      • Pratt DS
      • May Il
      Silo filler's disease in New York State.
      In those patients who survive the acute crisis, the usual clinical course of silo filler's disease is complete recovery and resolution of the pulmonary infiltrates, and pulmonary function returns to normal. Lymphocytic interstitial pneumonitis, seen in association with lymphoproliferative disorders, and pulmonary fibrosis are unlikely to occur in our patient. Likewise, autoimmune disease is not a known complication of silo filler's disease. Recurrence of acute silo filler's disease can be prevented by avoiding exposure to silo gas. Bronchiolitis obliterans, a serious complication, can occur 1 to 6 weeks after exposure.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Gurney JW
      • Unger JM
      • Dobry CA
      • Mitby JK
      • Von Essen SG
      Agricultural disorders of the lung.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      • Zwemer Jr, FL
      • Pratt DS
      • May Il
      Silo filler's disease in New York State.
      • Hirsch J
      • Fencel RM
      Case of the season: silo filler's disease in a patient with prior Swyer-James syndrome.
      Bronchiolitis obliterans is primarily an airway disease (as distinguished from bronchiolitis obliterans-organizing pneumonia). The precise incidence has not been determined. Douglas and associates postulated postulated that corticosteroid treatment has decreased the occurrence, possibly by preventing the proliferative cellular phase of bronchiolitis obliterans. When bronchiolitis obliterans develops after acute silo filler's disease, patients will have fever, cough, and dyspnea after a period of apparent recovery. Their chest roentgenogram usually reveals a diffuse reticulonodular or miliary pattern. Our patient was optimally treated for silo filler's disease. No classic clinical or laboratory features of bronchiolitis obliterans have developed.

      Discussion

      Silo filler's disease is a known occupational hazard among farmers. It occurs most frequently during the months of September and October in the northern hemisphere. Sudden deaths related to work in a silo were first described in 1914, and the interrelationship between this entity and inhalation of oxides of nitrogen was first reported in 1956.
      • Delaney Jr, LT
      • Schmidt HW
      • Stroebel CF
      Silo-filler's disease.
      Silos are upright cylindrical structures used for storage and fermentation of harvested field crops. The anaerobic environment within these silos allows bacteria to generate organic acids by the process of fermentation; thus, spoiling of the silage is deterred. Nitrates in the forage (chopped com, oats, and hay) are converted by bacteria to NO2 or NO, and these initial products further react with air to form NO2 and other higher oxides of nitrogen. These gases will begin to form a few hours after a silo has been filled and reach a peak concentration in 1 to 5 days.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      • Zwemer Jr, FL
      • Pratt DS
      • May Il
      Silo filler's disease in New York State.
      Dangerous concentrations will persist for several weeks. NO2 is a gas heavier than air with a characteristic reddish brown color and offensive “bleachlike” odor. The most common mode of exposure occurs when silos are opened within 48 hours after filling. Inhalation of NO2 gas causes various degrees of acute lung injury. This strong oxidant induces direct chemical injury to the bronchioles and alveoli by generation of free radicals, as well as the formation of destructive nitric and nitrous acids. Massive exposure can cause death by bronchiolar and laryngeal spasms or simple asphyxiation. Milder exposure usually results in upper airway and ocular irritation, cough, dyspnea, fatigue, lethargy, and even loss of consciousness. Pulmonary edema can develop within 3 to 30 hours after exposure.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      • Zwemer Jr, FL
      • Pratt DS
      • May Il
      Silo filler's disease in New York State.
      As mentioned earlier, a potential long-term sequela of silo filler's disease is bronchiolitis obliterans, a delayed-onset lung injury that may manifest as a recurrence of cough and dyspnea after a period of improvement. Chest roentgenograms show a diffuse reticulonodular or miliary pattern of infiltrates. Corticosteroid treatment has been associated with a reduced frequency of this delayed complication, although the exact natural incidence is ill-defined.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      • Zwemer Jr, FL
      • Pratt DS
      • May Il
      Silo filler's disease in New York State.
      Aside from corticosteroid treatment, the management of silo filler's disease has been primarily supportive. Patients with respiratory distress may require mechanical ventilatory support during the acute phase. Exposed patients with symptoms of dyspnea and evidence of hypoxemia, with or without pulmonary infiltrates, should be carefully observed and monitored for respiratory failure.
      The key to avoiding silo filler's disease is workplace precautions-that is, educating farmers to ventilate silos adequately before entering, maintain their ventilation equip ment, wear protective equipment when exposure is unavoidable, and recognize the signs of silo gas.
      • do Pico GA
      Hazardous exposure and lung disease among farm workers.
      • Douglas WW
      • Hepper NGG
      • Colby TV
      Silo-filler's disease.
      • Zwemer Jr, FL
      • Pratt DS
      • May Il
      Silo filler's disease in New York State.
      Our patient has undergone follow-up for 9 months, and prednisone therapy has been discontinued. His symptoms have gradually subsided, and improvement in results of pulmonary function tests and oxygenation (as shown by arterial blood gas studies) has been noted. His chest roentgenograms continue to reveal a mild restrictive pulmonary dysfunction as well as a patchy interstitial process-features that are inconsistent with the known complications of silo filler's disease. We suspect that he also has mild chronic hypersensitivity pneumonitis, which could perhaps be confirmed by a lung biopsy. The patient, however, has thus far declined such a procedure.

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        Hazardous exposure and lung disease among farm workers.
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        • Unger JM
        • Dobry CA
        • Mitby JK
        • Von Essen SG
        Agricultural disorders of the lung.
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        • Tukiainen HO
        • Terho EO
        Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung.
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        • Tukiainen HO
        • Terho EO
        Recovery of pulmonary function in farmer's lung: a five-year follow-up study.
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        • Lawton BR
        Pulmonary mycotoxicosis.
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        Organic dust toxicity (pulmonary mycotoxicosis) associated with silo unloading.
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        • Hepper NGG
        • Colby TV
        Silo-filler's disease.
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        • May Il
        Silo filler's disease in New York State.
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        Case of the season: silo filler's disease in a patient with prior Swyer-James syndrome.
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        Silo-filler's disease.
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