KEY POINTS
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Hypersensitivity pneumonitis is a type of interstitial lung disease that requires early diagnosis and treatment, as it can lead to progressive pulmonary fibrosis.
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Occupational history is essential when evaluating patients with respiratory symptoms.
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Causes of hypersensitivity pneumonitis include infectious agents; enzymes; animal, insect and vegetable proteins; chemicals and low molecular weight metals.
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Patients with respiratory symptoms who have been exposed to isocyanates should avoid exposure and be evaluated for asthma and hypersensitivity pneumonitis.
A 47-year-old woman presented to the hospital with a 3-month history of dry cough, wheezing, dyspnea, and intermittent fever. She had been briefly admitted 2 months earlier to treat a suspected lower respiratory tract infection or bronchitis; he had been prescribed inhalers (salbutamol, ipratropium) and antibiotics (ceftriaxone and azithromycin initially and then amoxicillin-clavulanic acid).
The patient had smoked 7 cigarettes a day for 12 years, but had quit 3 months earlier. He was not taking any regular medications, and his medical history was notable only for obstructive sleep apnea, which was treated with continuous positive airway pressure. He had no history of asthma, no pets, and no exposure to hot tubs, birds, or mold in the home. I had recently started working at a horticultural company where I made sets of plant caps, in which soil, adhesives, oil and water were combined to create stable molds for the seedlings.
The patient’s chest radiograph was normal at presentation and unchanged from her previous admission 2 months earlier. She was referred to the inpatient respirology service. When assessed, her respiratory rate was 22 breaths/min, oxygen saturation was 96% on room air, temperature was 35.9°C, heart rate was 104 beats/min and blood pressure was 129/86 mm Hg. He had bilateral wheezing and normal heart sounds. On examination, she had no evidence of finger clubbing, leg edema, rashes, or features suggestive of a connective tissue disorder. The emergency department physician ordered a computed tomography (CT) scan of the chest with contrast (pulmonary embolus protocol) to rule out pulmonary embolism.
Figure 1 is a representative chest CT image from the time of hospital admission, showing diffuse centrilobular ground-glass nodules in both lungs without any zonal predominance. There were no pulmonary emboli. The patient had substantial leukocytosis with neutrophilia (leukocytes 15.6 [normal 4.0–11.0] × 109/L, neutrophils 12.0 [normal 2.0–7.5] × 109/L), a normal eosinophil count (0.2 [normal 0.0–0.5] × 109/L) i una proteïna C reactiva elevada (49[normal<8mg/L)ComqueessospitavaunamalaltiapulmonarintersticialesvanordenarnivellsdefactorreumatoideanticossosantinuclearsianticossoscitoplasmàticsantineutròfilscitoplasmàticsiperinuclearsivansertotsnegatiusElsnivellsdepèptidnatriurèticcerebralitroponinaordenatsperunmetgedelserveid'urgènciesestavendinsdelslímitsnormalsenambduesvisitesal'hospitalL'espirometriavamostrarunareduccióproporcionadadelvolumespiratoriforçata1segon(FEV1)idelacapacitatvitalforçada(FVC)senseevidènciad'obstruccióElseuFVCerade213L(59%previst)elseuFEV1era154L(53%previst)ilasevarelacióFEV1:FVCeradel723%[normal<8mg/L)BecauseinterstitiallungdiseasewassuspectedrheumatoidfactorantinuclearantibodyandcytoplasmicandperinuclearantineutrophilcytoplasmicantibodylevelswereorderedandwereallnegativeBrainnatriureticpeptideandtroponinlevelsorderedbyanemergencydepartmentphysicianwerewithinnormallimitsonbothvisitstohospitalSpirometryshowedproportionatereductioninforceexpiratoryvolumeat1second(FEV1)andforcedvitalcapacity(FVC)withnoevidenceofobstructionHerFVCwas213L(59%predicted)herFEV1was154L(53%predicted)andherFEV1:FVCratiowas723%[normal<8mg/L)ComqueessospitavaunamalaltiapulmonarintersticialesvanordenarnivellsdefactorreumatoideanticossosantinuclearsianticossoscitoplasmàticsantineutròfilscitoplasmàticsiperinuclearsivansertotsnegatiusElsnivellsdepèptidnatriurèticcerebralitroponinaordenatsperunmetgedelserveid'urgènciesestavendinsdelslímitsnormalsenambduesvisitesal'hospitalL'espirometriavamostrarunareduccióproporcionadadelvolumespiratoriforçata1segon(FEV1)idelacapacitatvitalforçada(FVC)senseevidènciad'obstruccióElseuFVCerade213L(59%previst)elseuFEV1era154L(53%previst)ilasevarelacióFEV1:FVCeradel723%[normal<8mg/L)BecauseinterstitiallungdiseasewassuspectedrheumatoidfactorantinuclearantibodyandcytoplasmicandperinuclearantineutrophilcytoplasmicantibodylevelswereorderedandwereallnegativeBrainnatriureticpeptideandtroponinlevelsorderedbyanemergencydepartmentphysicianwerewithinnormallimitsonbothvisitstohospitalSpirometryshowedproportionatereductioninforcedexpiratoryvolumeat1second(FEV1)andforcedvitalcapacity(FVC)withnoevidenceofobstructionHerFVCwas213L(59%predicted)herFEV1was154L(53%predicted)andherFEV1:FVCratiowas723%
Figure 1:
Computed tomography (with contrast) of the chest of a 47-year-old woman with hypersensitivity pneumonitis at the time of hospital admission, showing diffuse centrilobular ground-glass opacities bilaterally.
Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy was performed. Bronchoalveolar lavage fluid from the right upper lobe was negative for malignant cells with few lymphocytes, eosinophils, and hemosiderin-laden macrophages. There were insufficient leukocytes to allow an accurate cell count. Cultures of fluid samples were negative for bacteria, fungi, and mycobacteria. A transbronchial biopsy of the right middle lobe showed chronic inflammation, diffuse fibrosis, and reactive epithelial proliferation.
Because of the clinical, radiographic, and bronchoscopic findings, the working diagnosis was hypersensitivity pneumonitis, most likely due to the patient’s occupational exposure to adhesives. He was started on intravenous solumedrol, experienced immediate relief of dyspnea and cough, and was discharged on prednisone (30 mg/d) with a 2-month tapering script. You were advised to avoid exposure to stickers. He was followed up after a few weeks in the outpatient clinic, with near resolution of symptoms.
The patient was seen in our occupational lung clinic 3 months after hospital discharge and we confirmed the occupational history. The patient had taken photographs with her cell phone of product labels she used at work, which confirmed that she was exposed to toluene diisocyanate (TDI), a compound found in polyurethane-based adhesives that can be highly immunogenic the lungs He said that when the cap assemblies were produced, the heated polyurethane adhesive often bubbled and aerosolized as it was poured into the soil mix. Despite using surgical masks and high-quality respirators, he continued to have respiratory symptoms.
Because the patient had been advised to stop exposure to TDI, her employer found her another job in a building without any isocyanate exposure. Prednisone therapy for 1 month resulted in marked improvement in symptoms and objective tests. Compared with values at the time of hospital admission, his pulmonary function test at 4 weeks after discharge showed a greater than 25% improvement in FVC and FEV1. His FVC was 2.86 L (79% predicted) and FEV1 was 2.38 L (82% predicted). In addition, his total lung capacity was 4.61 L (89% predicted) and diffusing capacity was 16.6 mL/min/mm Hg (78% predicted). Follow-up CT of her chest 1 month after starting prednisone showed complete clearance of the ground-glass nodules in the lungs (Figure 2). Outpatient allergy testing was negative for mold and other common environmental allergens.
Figure 2:
High-resolution computed tomography of the chest of a 47-year-old woman with hypersensitivity pneumonitis after treatment and antigen avoidance, showing complete resolution of centrilobular ground-glass opacities.
discussion
Occupational lung diseases are a common group of respiratory disorders. Although some of these diseases, such as asbestosis and silicosis, are almost always caused by occupational exposure, conditions such as asthma, chronic obstructive pulmonary disease, and interstitial lung disease are caused or aggravated by occupational exposure in 25% of cases.1 A classification. of interstitial lung disease is shown in Figure 3.
Figure 3:
Classification of selected types of interstitial lung disease (ILD). Note: IIP = idiopathic interstitial pneumonia. Adapted from Cottin and colleagues2 and published with permission from the European Respiratory Society.
Hypersensitivity pneumonitis, formerly known as extrinsic allergic alveolitis, is a type of interstitial lung disease caused by inhalation of antigens that induce non-immunoglobulin (Ig) E-mediated immune dysfunction in the lungs. If left untreated, hypersensitivity pneumonitis can lead to progressive pulmonary fibrosis with associated morbidity and death.3 About 20% of cases of hypersensitivity pneumonitis are caused by occupational exposure. Therefore, any patient suspected of having hypersensitivity pneumonitis based on history or imaging should be questioned.4 More than 200 antigens have been reported to cause hypersensitivity pneumonitis. Although it is frequently associated with farming, poultry, and mold, many cases of hypersensitivity pneumonitis do not have a clearly identified antigen.5 Exposure to diisocyanate, used in polyurethanes in our patient’s case , is commonly associated with asthma, but is also one of many agents known to cause occupational hypersensitivity pneumonitis (Table 1).5–7
Table 1:
Select the list of important agents known to cause occupational hypersensitivity pneumonitis*
Isocyanates are low molecular weight compounds classified as mono-, di- or polyisocyanates. Methylene diphenyl diisocyanate and TDI account for 95% of the diisocyanates used to create polyurethane polymers, and TDI is important in the production of paint coatings, adhesives, and insulating foam.8 Given its association with lung disease, patients with respiratory symptoms and antecedents. Exposure to diisocyanate-containing polyurethanes should be investigated with pulmonary function tests and chest imaging (preferably high-resolution CT) to rule out asthma and hypersensitivity pneumonitis when other diagnoses are less likely.
The diagnosis of hypersensitivity pneumonitis can be relatively difficult given the lack of standardized and validated diagnostic criteria. Recent consensus guidelines highlight important factors that support the diagnosis, such as exposure history, supportive CT, bronchoalveolar lavage indicating lymphocytosis, histopathologic findings (p. 10 According to expert panels, when high-resolution CT findings suggest hypersensitivity pneumonitis and there is known antigen exposure (either through history or laboratory findings), bronchoalveolar lavage lymphocytosis is sufficient to have a very confidence in the diagnosis. In its absence, however, a lung biopsy should be obtained to accurately diagnose hypersensitivity pneumonitis.9
In our patient, the combination of history, imaging, and biopsy results supported the diagnosis of hypersensitivity pneumonitis. The lack of lymphocytosis in the bronchoalveolar lavage could be due to early fibrosis seen on biopsy, as well as the patient’s smoking history. The onset of symptoms shortly after starting work and the dramatic…