Diagnosis Of Chronic Hypersensitivity Pneumonitis Research Articles

OCCUPATIONAL-HYPERSENSITIVITY PNEUMONITIS: A DIAGNOSIS NOT TO BE MISSED BY PROPER HISTORY TAKING

TOPIC: Occupational and Environmental Lung Diseases TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypersensitivity Pneumonitis (HP) is an inflammatory and/or fibrotic disease affecting the lung parenchyma. Radiographic or histopathological findings help to categorize HP as either fibrotic (mixed inflammatory plus fibrotic or purely fibrotic) or non-fibrotic (purely inflammatory), being the primary determinant of prognosis. Rarely acute respiratory decline can be the first manifestation of chronic HP that may develop within a wide timeframe from weeks to years of exposure. CASE PRESENTATION: A 38-year-old male with no comorbidities or smoking history, presented with one week of progressive shortness of breath. Further questions revealed that since childhood he was working in a car painting shop without using protective equipment. Vital signs: Temperature 36.9, pulse 98 beats/min, respiratory rate 22 breaths/min, blood pressure 116/96 mmHg, and oxygen saturation 37% on room air, improved to 98% via a non-rebreather mask. He was not in respiratory distress. Findings included diffuse bilateral crackles over the lung fields. CXR showed diffuse patchy bilateral alveolar opacities. WBC count and serum procalcitonin were within normal limits. SARS-CoV-2 PCR performed was negative. Chest CT showed extensive diffuse bilateral lung consolidations, ground-glass opacities, honeycombing, and prominent mediastinal lymph nodes. Given the patient symptoms, high-risk exposure to isocyanate which exists in paints, radiologic findings, and by ruling out infectious etiologies, the suspected diagnosis of HP was made and treatment with IV Methylprednisone 60mg twice daily initiated. After 2 days, clinical status improved and oxygen requirements decreased to 8 LPM via Nasal Cannula. Bronchoscopy showed erythema throughout the tracheobronchial tree. Bronchoalveolar lavage (BAL) was performed and cytology showed: Reactive bronchial cells (24% Lymphocytes, 31% macrophages, 44% neutrophils). Consequently, a diagnosis of chronic, non-fibrotic HP was confirmed. Finally, after completing 7 days of IV steroid treatment, he was discharged home with 2 LPM supplemental oxygen. Instructions regarding oral corticosteroid tapering over a 3 week-period were provided. DISCUSSION: Diagnosis of chronic HP is predominantly based on exposure identification, CT scan pattern, and bronchoscopic/histopathological findings. BAL in the majority of the patients with non-fibrotic chronic HP shows elevated cell count with greater than 20% lymphocytes and this group responds to steroid therapy significantly. CONCLUSIONS: We would like to emphasize the high value of taking detailed patient history to detect causative agent exposure. Unprotected exposure to isocyanate was the key leading to further investigation including performing BAL in our patient. We also recommend health care providers educate their patients regarding proper safety equipment use, in case of occupational exposure to HP inducers. Prevention is always better than cure! REFERENCE #1: Raghu G, Remy-Jardin M, Ryerson CJ, Myers JL, Kreuter M, Vasakova M, et. al. Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2020; 202(3):e36–e69. REFERENCE #2: Koster MA, Thomson CC, Collins BF, Jenkins AR, Ruminjo JK and Raghu G. Diagnosis of hypersensitivity pneumonitis in adults, 2020 clinical practice guideline: summary for clinicians. Ann Am Thorac Soc 2020. DISCLOSURES: no disclosure on file for Manish Gugnani; No relevant relationships by Irina Gutierrez Puentes, source=Web Response No relevant relationships by Julio Piedra Butina, source=Web Response No relevant relationships by Asieh TakallooBakhtiari, source=Web Response

Transbronchial biopsy in chronic hypersensitivity pneumonitis.

Introduction:The diagnosis of chronic hypersensitivity pneumonitis (CHP) is based on relevant exposure, tomographic findings and, in some cases, pathological data. The role of bronchoscopy is uncertain, especially in the fibrotic form of CHP.Aim:To analyze the yield of transbronchial biopsy (TBBx) in patients with CHP according to tomographic findings and to evaluate the importance of bronchoalveolar lavage (BAL) in the diagnostic approach.Methods:This retrospective study analyzed patients with CHP who underwent TBBx in São Paulo, Brazil. The TBBx findings were classified as characteristic (granulomas and/or multinucleated giant cells, associated or not with peribronchiolar infiltration of lymphocytes and plasma cells and bronchiolocentric distribution) and supportive (data indicative of small airway injury: peribronchiolar metaplasia, organizing pneumonia, and intra-alveolar foamy macrophages).Results:One hundred nine patients were included. The presence of characteristic findings of HP was seen in 16 patients (14.7%), and supportive findings were seen in 32 patients (29.4%), with a total yield of 44%. Pathological characteristic findings were more common in cases without fibrosis on high-resolution computed tomography (HRCT) (27.3% vs. 9.2%, p= 0.014), whereas the presence of supportive findings was more common in fibrotic HP (38.1% vs. 9.1%, p= 0.002). Fifty-two patients had differential cytology in BAL fluid. Lymphocytosis (> 20%) was present in 51.9% of the patients. There was no difference in the median lymphocyte count according to nonfibrotic and fibrotic tomographic findings on HRCT.Conclusion:TBBx and BAL fluid cytology have a role in CHP diagnosis.

Pneumonite de Hipersensibilidade Crónica: evolução de um Caso Clínico

INTRODUCTION Hypersensitivity pneumonitis (PH) or extrinsic allergic alveolitis is an inflammatory interstitial lung disease caused by recurrent exposure to a variety of environmental and/ or occupational antigens by immunologically susceptible individuals. The differential diagnosis with other interstitial lung diseases (ILD) is stimulating, but essential for a correct approach and implementation of appropriate therapy. CASE REPORT We present a case of a 55-year-old female worker, non-smoker, with no important pathological personal history. She had professional exposure to multiple paints (Gouache; Acrylics; Watercolors; Oil) inherent in her profession as an art teacher since she was 23 years old. After 24 years of performing these functions, without the use of proper personal protective equipment (protective mask, gloves, goggles, appropriate uniform), she develops a persistent cough, dyspnoea and fatigue, motivating observation in pulmonology consultation. Taking into account clinical, radiological and laboratory elements, she presented suggestive alterations of interstitial pulmonary pathology, and the diagnosis of Chronic Hypersensitivity Pneumonitis was assumed in a Multidisciplinary Group Consultation later assumed and characterized as an Occupational Disease. In the follow-up, the causal agent of the disease was removed, having the worker been mobilized internally, assuming functions associated with school coordination, for which she was able to work. Since 2011 under immunosuppression therapy with Prednisolone, Azathioprine from July 2014 to August 2016 and Mycophenolate Mofetil since March 2019, having remained clinically and functionally stable until today, without the need for oxygen therapy. As complementary diagnostic tests it has a respiratory function in 2019: FEV1 51%; FVC 55%; 73% TLC. 33% DLCO; DLCO/VA: 51%. Chest CT with scattered, bilateral ground glass densification areas; some cystic images, bilaterally, corresponding to areas of bronchial ectasia/ fibrosis; traction bronchiectasis, mainly in the upper lobes and the middle lobe; reticulation areas in the anterior right pulmonary field; calcified granuloma in the lower right lobe and upper left lobe; infracentimetric nodularities at both apexes. DISCUSSION/ CONCLUSION Chronic HP is an irreversible disease. Removal of the disease-causing antigen and immunosuppressive therapy are the usual interventions in these cases. In this worker, once the relationship between the pathology and the causal agent of the disease was assumed, was assigned a definitive incapacity for the current job, having been replaced in another compatible activity within the same company. Thus, occupational health surveillance becomes essential in the prevention/ attenuation of this occupational disease.

Histology is critical but not always for the diagnosis of chronic hypersensitivity pneumonitis

The diagnosis of chronic hypersensitivity pneumonitis (CHP) is often based on the pathology, but evidence is scarce that a pathological diagnosis of CHP may mislead the multidisciplinary diagnosis. We enrolled patients from the consultation case archive whose pathological findings were suggestive of CHP but had a multidisciplinary diagnosis of non-CHP. The histopathological slides were sent to another pathologist, and the ones confirmed with CHP were sent for an additional multidisciplinary discussion (MDD). We examined clinicopathological features of the cases confirmed to be non-CHP through MDD. Among the 243 cases, five were diagnosed as non-CHP through an additional MDD. The most common causes of discrepancy were the presence of strong autoimmune features, a low lymphocyte level in the bronchoalveolar lavage fluid, and a lack of nodular shadow or mosaic attenuation on computed tomography. Cases of suspected CHP on pathology may be determined to be non-CHP through MDD.

Multidisciplinary team approach on a case of bilateral interstitial pneumonia

Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by exposure to a wide variety of organic particles. In this article, we report a rare case of a 44-year-old male patient with cough and shortness of breath for more than 4 years and exacerbation for 1 month. The findings of lung computed tomography (CT) and pathology supported a diagnosis of chronic HP. The patient had a history of ulcerative colitis for 5 years, and used to take salazosulfapyridine more than 4 years since 2013. We organized domestic and foreign experts to discuss the diagnosis and treatment of this case. The final clinical diagnosis was chronic interstitial pneumonia [related to sulfasalazine or inflammatory bowel disease (IBD) itself], pulmonary infections. It is recommended to discontinuation of sulfasalazine and oral administration of glucocorticoids and required long-term follow-up.

High-resolution CT features distinguishing usual interstitial pneumonia pattern in chronic hypersensitivity pneumonitis from those with idiopathic pulmonary fibrosis.

Radiologic diagnosis of chronic hypersensitivity pneumonitis (CHP) presenting a usual interstitial pneumonia (UIP) pattern is challenging. The aim of this study was to identify the high-resolution CT (HRCT) findings which are useful to discriminate CHP-UIP from idiopathic pulmonary fibrosis (IPF). This study included 49 patients with well-established bird-related CHP-UIP, histologically confirmed, and 49 patients with IPF. Two groups of observers independently assessed HRCT, evaluated the extent of each abnormal HRCT finding. When their radiological diagnosis was CHP-UIP, they noted the HRCT findings inconsistent with IPF. Correct CT diagnoses were made in 79% of CHP-UIP and 53% of IPF. Although no apparent difference was seen in the extent of each HRCT finding, upper or mid-lung predominance, extensive ground-glass abnormality, and profuse micronodules were more frequently pointed out as inconsistent findings in CHP-UIP than IPF (p = 0.007, 0.010, 0.001, respectively). On regression analysis, profuse micronodules [OR 13.34 (2.85-62.37); p = 0.001] and upper or mid-lung predominance of findings [OR 2.86 (1.16-7.01); p = 0.022] remained as variables in the equation. In this cohort, some IPF cases were misdiagnosed as CHP-UIP. Profuse micronodules and upper or mid-lung predominance are important clues for the differentiation of CHP-UIP from IPF.

HYPERSENSITIVITY PNEUMONITIS DUE TO AN OUTDOOR ANTIGEN IN THE HOME

Introduction Common etiologies of hypersensitivity pneumonitis (HP) include avian, bacterial, fungal, occupational, and agricultural exposures. We present a case of HP to an external avian antigen that became present in the home. Case description A 69-year-old non-smoking retired teacher with adult-onset asthma presented with an 18-month history of dry cough without improvement with ICS/LABA or H2 antagonists. She had been treated with prednisone 10mg daily for four months with difficulty tapering due to cough. She denied fevers or weight loss. She had no pets although previously had a bird feeder in her yard but denied pigeon exposure. Exam was notable for diffuse rhonchi. Chest CT showed patchy ground glass densities. Spirometry demonstrated FEV1 1.70 (74%), FVC 2.41 (80%), FEV1/FVC 0.71. An initial HP panel was negative, but IgG sent later for pigeon droppings was positive. Due to high suspicion for HP, patient's home furnace filter was analyzed which showed a precipitin band to pigeon droppings. After changing home filters and avoiding pigeons, her cough resolved, and prednisone was tapered to 1mg. Discussion Organic material from pigeon droppings outdoors can become aerosolized and compromise indoor air quality. The diagnosis of chronic HP may be difficult to confer in patients with persistent asthma. Our patient's refractory cough, CT findings, serum IgG and filter pigeon precipitins, and symptom resolution with avoidance met criteria for HP. Despite not owning or working with birds and a negative commercial lab HP panel, a high suspicion allowed for identification of an unsuspecting outdoor source within the home.

Identification of Diagnostic Criteria for Chronic Hypersensitivity Pneumonitis: An International Modified Delphi Survey.

Current diagnosis of chronic hypersensitivity pneumonitis (cHP) involves considering a combination of clinical, radiological, and pathological information in multidisciplinary team discussions. However, this approach is highly variable with poor agreement between centers. We aimed to identify diagnostic criteria for cHP that reach consensus among international experts. A 3-round modified Delphi survey was conducted between April and August 2017. Forty-five experts in interstitial lung disease from 14 countries participated in the online survey. Diagnostic items included in round 1 were generated using expert interviews and literature review. During rounds 1 and 2, experts rated the importance of each diagnostic item on a 5-point Likert scale. The a priori threshold of consensus was ≥ 75% of experts rating a diagnostic item as very important or important. In the third round, experts graded the items that met consensus as important and provided their level of diagnostic confidence for a series of clinical scenarios. Consensus was achieved on 18 of the 40 diagnostic items. Among these, experts gave the highest level of importance to the identification of a causative antigen, time relation between exposure and disease, mosaic attenuation on chest imaging, and poorly formed non-necrotizing granulomas on pathology. In clinical scenarios, the diagnostic confidence of experts in cHP was heightened by the presence of these diagnostic items. This consensus-based approach for the diagnosis of cHP represents a first step towards the development of international guidelines for the diagnosis of cHP.

P239 Diagnostic potential of MMP-1 and SP-A as biomarkers to distinguish chronic hypersensitivity pneumonitis from Idiopathic pulmonary fibrosis

Introduction: Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease caused by a wide variety of organic particles. In general, the diagnosis of chronic HP represents a challenge for clinicians that need to use a constellation of clinical, laboratory, radiographic and pathological data to assess a confident diagnosis. Importantly, the clinical features cHP can be indistinguishable from those observed in idiopathic pulmonary fibrosis (IPF). Objective: To determine whether serum levels of surfactant protein A (SP-A) and matrix metalloprotease-1 (MMP-1) may help to differentiate cHP from IPF. Methods: This was a cross-sectional study including patients with IPF (n = 31), cHP (n = 31) and 17 healthy subjects. SP-A and MMP-1 serum levels were determined by ELISA and were evaluated for the differential diagnosis between HP and IPF, and also correlated with values of pulmonary function tests at diagnosis. Results: MMP-1 and SP-A were significantly elevated in cHP compared with the other two groups. MMP-1 (HP= 11.7 ± 14 ng/ml versus FPI= 16 ± 20.7 ng/ml, p< 0.001) and versus Controls= (0.4 ± 0.3 ng/ml, p < 0.0001), ANOVA between groups < 0.0001. SP-A (HP= 74 ± 30 pg/ml versus FPI= 54 ± 20 pg/ml, p< 0.02) and versus Controls= (35 ± 6 pg/ml, p < 0.0001), ANOVA between groups < 0.0001. There was no correlation between MMP-1 or SP-A levels with the abnormalities in pulmonary function tests. Conclusions: Our findings indicate that patients with cHP display the highest concentration of MMP-1 and SP-A which may be useful biomarkers to distinguish it from IPF.

Utility of Exhaled Nitric Oxide Fraction for the Diagnosis of Hypersensitivity Pneumonitis

There is very little evidence of the utility of the exhaled fraction of NO (FeNO) for the diagnosis of interstitial lung disease and nearly all of it is related with connective tissue disease. Some authors have suggested that in patients with hypersensitivity pneumonitis (HP), evolution to pulmonary fibrosis may be mediated by a Th2 mechanism, which could redound in a potential utility of FeNO. The aim of this study was to investigate the values of FeNO before and after antigenic exposure with the specific inhalation challenge (SIC) and to analyze its potential utility for the diagnosis of HP. It was a prospective, cross-sectional study of all patients older than 18 years referred to our center for suspected chronic HP between May 2012 and May 2014 and who underwent a SIC. FeNO was collected before and after SIC. The study sample comprised 25 patients. Eleven were diagnosed with chronic HP; six had been exposed to avian proteins and five to fungal agents. Of these 11 patients, seven had positive SICs. In the 14 patients with diagnoses other than HP, all the SICs were negative. No significant differences in baseline characteristics were observed according to HP diagnosis, except in the BAL lymphocyte count. No differences were found after the test in patients diagnosed with HP; nor were there differences in baseline FeNO in patients diagnosed with HP and those who received alternative diagnoses. The results suggest that FeNO measurement is not useful for the diagnosis of chronic HP.

Antigen avoidance tests for diagnosis of chronic hypersensitivity pneumonitis.

Chronic hypersensitivity pneumonitis (HP) is induced by the inhalation of specific antigens. Patients with chronic HP may be able to improve their prognosis by avoiding these antigens. Chronic HP is often difficult to distinguish from idiopathic interstitial pneumonias (IIPs). This study was performed to find out how antigen avoidance tests contribute to the diagnosis of chronic HP. A retrospective analysis was conducted on 265 patients who underwent 2-week antigen avoidance tests between April 2002 and March 2012. The patients were classified into the following categories: acute HP, chronic HP, collagen vascular disease-associated interstitial pneumonia (CVD-IP), lung dominant connective tissue disease (LD-CTD), and IIPs. The following seven clinical parameters were evaluated: vital capacity, alveolar-arterial oxygen pressure difference, Krebs von den Lungen-6, surfactant protein-D, white blood cell count, C-reactive protein, and body temperature. These parameters were compared between the chronic HP group and a control group consisting of CVD-IP, LD-CTD, and IIPs. One-hundred and ninety-six patients with chronic HP and 43 control subjects were evaluated. All clinical parameters improved significantly in the chronic HP group but showed no significant changes in the control group. Four of the parameters changed significantly compared with the control group. Diagnostic criteria established using these data had a sensitivity of 51.0% and a specificity of 80.7%. It was difficult to diagnose chronic HP based solely on 2-week antigen avoidance tests; however, improved clinical parameters among patients supported the diagnosis of HP.

Validation of inhalation provocation test in chronic bird-related hypersensitivity pneumonitis and new prediction score.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of any of a wide variety of antigens. For example, bird-related HP (BRHP) results from the inhalation of avian antigens. The clinical features of chronic HP, including imaging and histological findings, are similar to those of idiopathic pulmonary fibrosis. Despite its status as the "gold standard," the inhalation provocation test (IPT) is rarely performed, because the methods and the criteria are not standardized. In 2000, we reported the utility of IPT for pigeon dropping extracts. The purpose of the current study was to validate the utility and safety of the test, and to differentiate chronic HP from other interstitial lung diseases. A total of 28 patients with chronic BRHP and 19 control subjects were evaluated in this retrospective study. We validated the previous criteria and proposed new criteria using prediction scores. In the IPT using pigeon dropping extracts, the previous criteria showed a sensitivity of 78.6% and a specificity of 94.7% in this retrospective study. The increases in the peripheral white blood cell count and C-reactive protein levels are good indicators of a positive response to the inhalation challenge. We propose the use of the IPT prediction score (∆WBC [%] + 2 × ∆P[a - a]O2 [mm Hg], where WBC is white blood cell) and the prediction rule, which showed high sensitivity and specificity values of 92.9 and 94.7%, respectively. Two (1.5%) out of a total of 130 subjects who underwent the tests required treatment after the challenge. The IPT is a useful and safe tool for the diagnosis of chronic HP. The IPT prediction score that we have proposed has high sensitivity and specificity in the diagnosis of chronic BRHP.

Lesson of the month: extrinsic allergic (bronchiolo)alveolitis and metal working fluids

One of us was asked to consider a diagnosis of occupational asthma for a man who had worked for 20 years as a metal turner in a large, modern factory...

Making an Accurate Diagnosis of Chronic Hypersensitivity Pneumonitis

Chronic hypersensitivity pneumonitis (HP) arises from repeated exposure to causative antigens. Although HP can be challenging to diagnose, it is important to differentiate from idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia. HP has a unique management approach and portends a unique prognosis. The present article summarizes the recent published literature on chronic HP and highlights the features that may be helpful in distinguishing it from other chronic interstitial lung diseases.

Lung Cancer in Chronic Hypersensitivity Pneumonitis

Background: So far, the association of lung cancer with chronic hypersensitivity pneumonitis (CHP) has not been studied. Objective: We examined the prevalence and revealed clinical features of lung cancer in CHP. Methods: We retrospectively reviewed the medical records from 1994 through 2005 and identified 11 patients (15 lesions) with lung cancer among 104 patients with CHP. Their clinical features and histopathological findings were analyzed. Results: Ten men and 1 woman with a median age of 68.9 years were included. All patients had a smoking history. The most prevalent histopathological type of lung cancer was squamous cell carcinoma (53%), and all tumors were located in the peripheral region of the lung. Four patients suffered from lung cancer after the diagnosis of CHP and 1 patient had lung cancer before the diagnosis of CHP. The histological pattern of CHP showed a predominantly usual interstitial pneumonia-like lesion. Tumors were located adjacent to honeycombing in 7 (47%) of 15 lesions, bullae in 4 (27%) lesions, and relatively normal lung in 4 lesions. Conclusions: Since the prevalence of lung cancer in CHP seems to be high (10.6%) as seen in idiopathic pulmonary fibrosis, physicians should be aware of the possible complication of lung cancer in CHP.

Chronic hypersensitivity pneumonitis: use of CT in diagnosis.

In its subacute or chronic form, hypersensitivity pneumonitis is often difficult to distinguish clinically and physiologically from other idiopathic diffuse lung diseases. The aim of this study was to identify high-resolution CT features that allow distinction of chronic hypersensitivity pneumonitis from other chronic diffuse parenchymal lung diseases. Six patients with chronic hypersensitivity pneumonitis were examined with pulmonary function testing, bronchoalveolar lavage, lung biopsy, chest radiography, and high-resolution CT. The chest radiographs and high-resolution CT scans were reviewed independently by three observers without knowledge of the patients' clinical status. Discrepancies between the observers were resolved by consensus. The chest radiographs revealed normal lung volumes with a combination of abnormalities: a mixed alveolar/interstitial pattern in five cases, peribronchiolar thickening in three, a diffuse granular pattern in one, and a linear fibrotic pattern in one. In general, the high-resolution CT scans showed more abnormalities than were apparent on the plain chest radiographs. High-resolution CT revealed centrilobular, peribronchiolar, indistinct nodular opacities, of various numbers, in all cases. Four cases had areas of ground-glass density, three cases had lobular areas of hyperlucency, and one case had areas of pulmonary fibrosis and honeycombing. We confirm that high-resolution CT can most clearly show the type and distribution of parenchymal abnormalities in patients with hypersensitivity pneumonitis. Importantly, although not pathognomonic, the high-resolution CT finding of centrilobular, peribronchiolar, indistinct nodules should suggest the diagnosis of chronic hypersensitivity pneumonitis.