The effectiveness and pharmacoeconomic study of using different corticosteroids in the treatment of hypersensitivity pneumonitis.

PURPOSE: Interstitial lung diseases (ILDs) are caused by inflammation and/or fibrosis of alveolar walls resulting in impaired gas exchange. Hypersensitivity pneumonitis (HP) is the third most common type of ILDs. Corticosteroids are the mainstay treatment for HP. The use of intramuscular (IM) betamethasone or intravenous (IV) dexamethasone as weekly pulse doses has shown higher benefit than daily oral prednisolone for HP patients. The aim of this study is to directly compare different corticosteroids in terms of effectiveness and in monetary values and perform an economic evaluation. METHODS: One hundred and seven patients were tested for pulmonary function tests (PFTs) and inflammatory markers to assess the treatment effectiveness. A cost-effectiveness analysis (CEA) was performed. ICERs between 3 treatment groups were calculated. RESULTS: Post treatment, Krebs von den Lungen-6 (KL-6) levels significantly improved in betamethasone group from 723.22 ± 218.18 U/ml to 554.48 ± 129.69 U/ml (p = 0.001). A significant improvement in erythrocyte sedimentation rate (ESR) occurred in the dexamethasone group from 56.12 ± 27.97 mm to 30.06 ± 16.04 mm (p = 0.048). A significant improvement in forced expiratory volume (FEV1), forced vital capacity (FVC) and six-minute walk distance (6MWD) was observed within the three treatment groups. A significant improvement in oxygen desaturation percentage (SpO2) occurred within dexamethasone and betamethasone groups. Betamethasone and dexamethasone were found more cost-effective than prednisolone as their ICERs fell in quadrant C. Furthermore, ICER between betamethasone and dexamethasone was performed; a small difference in cost was found compared to the higher benefit of betamethasone. CONCLUSION: Betamethasone and dexamethasone were found to be more effective than prednisolone in improving the inflammatory reaction and the clinical features of HP patients. Betamethasone was found to be the best intervention in terms of cost against the effect.

Assessment of clinical relevance of antigen improves diagnostic accuracy of hypersensitivity pneumonitis.

BACKGROUND: Exposure assessment is integral to the diagnosis of hypersensitivity pneumonitis (HP). Although the clinical relevance of exposed antigens is essential for the assessment, many of the previous guidelines or reports have only evaluated simple exposure histories or immunological tests. To overcome this problem, the Exposure Assessment Form (EAF) was developed as an assessment tool for classifying the exposure grade from G0 to G4. The EAF was modified from the description in the Japanese clinical practice guide 2022 for HP published by the Japanese Respiratory Society. METHODS: One hundred and seventy-two consecutive patients with interstitial lung disease who underwent multidisciplinary discussion (MDD) at our hospital were retrospectively examined. We assessed whether the use of the EAF improved the diagnostic performance of the international guideline of HP. We also evaluated whether the exposure grade affected the prognosis of HP. RESULTS: Even when a HP diagnosis was made with a confidence of 70% or higher according to the international guideline, less than half of these cases resulted in a final diagnosis of HP when the exposure grades were lower than G3. When the result of the EAF was integrated into the exposure definition of the international guideline, the specificity of the diagnostic performance improved, while sensitivity was maintained. Furthermore, HP patients with an exposure grade of G3 or higher showed a tendency to take a longer time to initiate medication. CONCLUSIONS: This is the first study to evaluate the clinical relevance of possible antigens using the EAF. Assessing the exposure grade prevents overdiagnosis and improves the diagnostic performance of the international guideline.

Idiopathic pulmonary fibrosis in the United States: time to diagnosis and treatment.

OBJECTIVE: Create a timeline of diagnosis and treatment for IPF in the US. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed in collaboration with the OptumLabs Data Warehouse using an administrative claims database of Medicare Fee for Service beneficiaries. Adults 50 and over with IPF were included (2014 to 2019). EXPOSURE: To focus on IPF, the following diagnoses were excluded: post-inflammatory fibrosis, hypersensitivity pneumonitis, rheumatoid arthritis, sarcoidosis, scleroderma, and connective tissue disease. MAIN OUTCOMES AND MEASURES: Data were collected from periods prior, during, and following initial clinical diagnosis of IPF. This included prior respiratory diagnoses, number of respiratory-related hospitalizations, anti-fibrotic and oxygen use, and survival. RESULTS: A total of 44,891 with IPF were identified. The most common diagnoses prior to diagnosis of IPF were upper respiratory infections (47%), acute bronchitis (13%), other respiratory disease (10%), chronic obstructive pulmonary disease and bronchiectasis (7%), and pneumonia (6%). The average time to a diagnosis of IPF was 2.7 years after initial respiratory diagnosis. Half of patients had two or more respiratory-related hospitalizations prior to IPF diagnosis. Also, 37% of patients were prescribed oxygen prior to diagnosis of IPF. These observations suggest delayed diagnosis. We also observed only 10.4% were treated with anti-fibrotics. Overall survival declined each year after diagnosis with median survival of 2.80 years. CONCLUSIONS AND RELEVANCE: Our retrospective cohort demonstrates that IPF is often diagnosed late, usually preceded by other respiratory diagnoses and hospitalizations. Use of available therapies is low and outcomes remain poor.

Exposure Assessment Tools for Hypersensitivity Pneumonitis. An Official American Thoracic Society Workshop Report.

This report is based on proceedings from the Exposure Assessment Tools for Hypersensitivity Pneumonitis (HP) Workshop, sponsored by the American Thoracic Society, that took place on May 18, 2019, in Dallas, Texas. The workshop was initiated by members from the Environmental, Occupational, and Population Health and Clinical Problems Assemblies of the American Thoracic Society. Participants included international experts from pulmonary medicine, occupational medicine, radiology, pathology, and exposure science. The meeting objectives were to 1) define currently available tools for exposure assessment in evaluation of HP, 2) describe the evidence base supporting the role for these exposure assessment tools in HP evaluation, 3) identify limitations and barriers to each tool's implementation in clinical practice, 4) determine which exposure assessment tools demonstrate the best performance characteristics and applicability, and 5) identify research needs for improving exposure assessment tools for HP. Specific discussion topics included history-taking and exposure questionnaires, antigen avoidance, environmental assessment, specific inhalational challenge, serum-specific IgG testing, skin testing, lymphocyte proliferation testing, and a multidisciplinary team approach. Priorities for research in this area were identified.

Assessment and Management of Occupational Hypersensitivity Pneumonitis.

The diagnosis and treatment of occupational hypersensitivity pneumonitis (OHP) remain complex and challenging in the absence of diagnostic gold standards or clinical guidelines. This review provides an update of the recent literature regarding the different presentations of OHP and the diagnostic yield and value of the diagnostic tests currently available, which include occupational and medical history, laboratory tests (serum-specific immunoglobulins, environmental sampling), imaging, bronchoalveolar lavage, transbronchial biopsy, transbronchial cryobiopsy, surgical lung biopsy, and specific inhalation challenges. These tools provide a precise differential diagnosis within the framework of interstitial lung diseases. However, among the chronic fibrotic forms, distinguishing OHP from sarcoidosis, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis remains a diagnostic challenge. Avoidance of exposure is pivotal for OHP management, whereas corticosteroids are fundamental in the pharmacological approach to this disease. In addition, studies describing the long-term benefits of immunosuppressive and antifibrotic agents have increased the use of these treatments in OHP.

Chronic hypersensitivity pneumonitis in the southeastern United States: an assessment of how clinicians reached the diagnosis.

BACKGROUND: Chronic hypersensitivity pneumonitis (cHP) is a disease caused by exposure to inhaled environmental antigens. Diagnosis of cHP is influenced by the awareness of the disease prevalence, which varies significantly in different regions, and how clinicians utilize relevant clinical information. We conducted a retrospective study to evaluate how clinicians in the Southeast United States, where the climate is humid favoring mold growth, diagnosed cHP using items identified in the international modified Delphi survey of experts, i.e., environmental exposure, CT imaging and lung pathology, METHODS: We searched Duke University Medical Center database for patients over the age of 18 with a diagnosis of cHP (ICD-9 code: 495) between Jan. 1, 2008 to Dec. 31, 2013 using a query tool, Duke Enterprise Data Unified Content Explorer (DEDUCE). RESULTS: Five hundred patients were identified and 261 patients had cHP confirmed in clinic notes by a pulmonologist or an allergist. About half of the patients lived in the Research Triangle area where our medical center is located, giving an estimated prevalence rate of 6.5 per 100,000 persons. An exposure source was mentioned in 69.3% of the patient. The most common exposure sources were environmental molds (43.1%) and birds (26.0%). We used Venn diagram to evaluate how the patients met the three most common cHP diagnostic criteria: evidence of environmental exposures (history or precipitin) (E), chest CT imaging (C) and pathology from lung biopsies (P). Eighteen patients (6.9%) met none of three criteria. Of the remaining 243 patients, 135 patients (55.6%) had one (E 35.0%, C 3.3%, P 17.3%), 81 patients (33.3%) had two (E + C 12.3%, E + P 17.3%, C + P 4.9%), and 27 patients (11.1%) had all three criteria (E + C + P). Overall, 49.4% of patients had pathology from lung biopsy compared to 31.6% with CT scan. CONCLUSIONS: Environmental mold was the most common exposure for cHP in the Southeast United States. Lung pathology was available in more than half of cHP cases in our tertiary care center, perhaps reflecting the complexity of referrals. Differences in exposure sources and referral patterns should be considered in devising future diagnostic pathways or guidelines for cHP.

A Systematically Derived Exposure Assessment Instrument for Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is an immune-mediated interstitial lung disease (ILD) caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis. METHODS: A list of potential causative exposures were derived from a systematic review of the literature. A Delphi method was applied to an international panel of ILD experts to obtain consensus regarding technique for the elicitation of exposure to antigens relevant to a diagnosis of CHP. The consensus threshold was set at 80% agreement, and median ≤ 2, interquartile range = 0 on a 5-point Likert scale (1, strongly agree; 2, tend to agree; 3, neither agree nor disagree; 4, disagree; 5, strongly disagree). RESULTS: In two rounds, 36/40 experts participated. Experts agreed on 18 exposure items to ask every patient with suspected CHP. Themes included CHP inducing exposures, features that contribute to an exposure's relevance, and quantification of a relevant exposure. Based on the results from the literature review and Delphi process, a CHP exposure assessment instrument was derived. Using cognitive interviews, the instrument was revised by patients with ILD for readability and usability. CONCLUSIONS: This Delphi survey provides items that ILD experts agree are important to ask in all patients presenting with suspected CHP and provides basis for a systematically derived CHP exposure assessment instrument. Clinical utility of this exposure assessment instrument may be affected by different local prevalence patterns of exposures. Ongoing research is required to clinically validate these items and consider their impact in more geographically diverse settings.

An Incidental Finding at Transplant Assessment: Case Report.

A 43-year-old woman with chronic hypersensitivity pneumonitis was referred for lung transplant assessment. An echocardiogram as part of her work-up revealed a large left atrial myxoma, presenting a conundrum on how best to manage her combined pathology. Because of the level of pulmonary disease, early intervention to remove the myxoma was not thought be viable without postoperative support. Use of extracorporeal membrane oxygenation to bridge patients for lung transplant is feasible, yet risks increased perioperative mortality. We present the first reported case of simultaneous cardiac myxoma removal and lung transplant.

Costs of Workplace Productivity Loss in Patients With Fibrotic Interstitial Lung Disease.

BACKGROUND: Fibrotic interstitial lung diseases (ILDs) are highly morbid chronic disorders that frequently occur in working age individuals. The goal of this study was to determine workplace productivity loss, its determinants, and its estimated costs in patients with fibrotic ILD. METHODS: Patients with idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, idiopathic nonspecific interstitial pneumonia, or unclassifiable ILD were identified from the six-center Canadian Registry for Pulmonary Fibrosis (CARE-PF). The Work Productivity and Activity Impairment questionnaire was used to determine health-related productivity loss. Independent predictors of low workplace productivity were identified by using multivariate regression. Patient data were compared with Canadian population census data. The average productivity loss (hours per week) and the individual's hourly wage were used to estimate the costs of productivity loss. RESULTS: Of 650 eligible patients, 148 (23%) were employed. Productivity loss was reported by 55% of employed patients with an average productivity loss of 7.8 ± 0.9 h per week (2.3 ± 0.6 h per week related to absenteeism and 5.5 ± 0.6 h per week related to presenteeism). Employment among patients with ILD aged 25 to 54 years was 23% lower than the age- and sex-matched general Canadian population (60% vs 83%; P < .001). Employment among patients with ILD aged ≥ 55 years was 18% lower than in the age- and sex-matched population (20% vs 38%; P < .001). Dyspnea and cough were independent predictors of workplace productivity loss. Estimated annual costs of productivity loss were 11,610 Canadian dollars per employee with ILD. CONCLUSIONS: Workplace productivity loss is common in fibrotic ILD, strongly correlated with symptom severity, and associated with significant cost.

Burden of serious fungal infections in the Czech Republic.

We have estimated the number of serious fungal infections in the Czech Republic. All published epidemiology papers reporting Czech fungal infection rates were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations. Population statistics were obtained from the 2011 Census data, prevalence and incidence data for at-risk conditions were obtained from publicly accessible healthcare statistics and relevant surveys. We estimate that 152,840 Czech women suffer with recurrent vaginal thrush. Allergic bronchopulmonary aspergillosis is likely in 4739 adults and 6581 more have severe asthma with fungal sensitisation. Hypersensitivity pneumonitits secondary to fungi is estimated in 1050 cases and 365 people may have chronic pulmonary aspergillosis. Oesophageal candidiasis is estimated in 210 HIV-positive people. There are 12 cases of Pneumocystis pneumonia in HIV population and 60 more cases in non-HIV population. There are an estimated 526 cases of candidaemia, 79 cases of Candida peritonitis and 297 cases of invasive aspergillosis a year. About 176,000 (1.67%) Czech people suffer from severe fungal infections each year, predominantly from recurrent vaginitis and allergic respiratory conditions. Substantial uncertainty surrounds these estimates except for invasive aspergillosis in haematology and candidaemia in critical care.

Workers' compensation for occupational respiratory diseases.

The respiratory system is one of the most important body systems particularly from the viewpoint of occupational medicine because it is the major route of occupational exposure. In 2013, there were significant changes in the specific criteria for the recognition of occupational diseases, which were established by the Enforcement Decree of the Industrial Accident Compensation Insurance Act (IACIA). In this article, the authors deal with the former criteria, implications of the revision, and changes in the specific criteria in Korea by focusing on the 2013 amendment to the IACIA. Before the 2013 amendment to the IACIA, occupational respiratory disease was not a category because the previous criteria were based on specific hazardous agents and their health effects. Workers as well as clinicians were not familiar with the agent-based criteria. To improve these criteria, a system-based structure was added. Through these changes, in the current criteria, 33 types of agents and 11 types of respiratory diseases are listed under diseases of the respiratory system. In the current criteria, there are no concrete guidelines for evaluating work-relatedness, such as estimating the exposure level, latent period, and detailed examination methods. The results of further studies can support the formulation of detailed criteria.

Clinical assessment of occupational asthma and its differential diagnosis.

Occupational asthma (OA) is defined as asthma caused by sources and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace. Two types of OA are distinguished based on their appearance after a latency period or not. The most frequent type appears after a latency period leading to sensitization; the clinical assessment of this type of OA is the topic of this review. The differential diagnosis of OA is also reviewed, including work-exacerbated asthma, eosinophilic bronchitis, hyperventilation syndrome, vocal cord dysfunction, bronchiolitis, and other causes of dyspnea or cough.

Simple flow cytometric protocol of CD4+/CD8+ lymphocyte ratio assessment in bronchoalveolar lavage fluids from patients with interstitial lung diseases.

OBJECTIVE: To validate the fast and accurate flow cytometric (FCM) protocol using blood-standardized antibodies for alveolar lymphocyte subtyping with respect to standard immunocytochemistry (IC). STUDY DESIGN: FCM and IC were applied to immunophenotype T cell subsets in bronchoalveolar lavage (BAL) fluids from patients with interstitial lung diseases. Diagnostic BAL specimens from 50 patients with suspected sarcoidosis, idiopathic pulmonary fibrosis, and hypersensitivity pneumonitis were evaluated by both IC and FCM. In FCM, CD4+ and CD8+ T cells were identified by light scatter gating with CD3 selection using basic tricolor cytometer. RESULTS: Relative amounts of CD4+, CD8+ T cells, and CD4+/CD8+ ratios demonstrated by the FCM showed excellent, significant correlations with IC results. FCM values did not differ significantly from IC results. However, the sensitivity and specificity of conventional IC staining were not sufficient to assess CD4+/ CD8+ ratio in most idiopathic pulmonary fibrosis cases. Additionally, performing IC immunophenotyping in BAL samples with low lymphocyte content introduced a remarkable error into CD4+/CD8+ ratio assessment. CONCLUSION: FCM allowed reliable, precise, and fast T-cell subset measurement in all BAL samples, overcoming the IC disadvantages. Our validated FCM protocol provides diagnostically relevant CD4+/CD8+ ratio determination by simple light scatter gating strategy with CD3 selection.

Needs and opportunities for research in hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) develops after inhalation of many different environmental antigens, causing variable clinical symptoms that often make diagnosis uncertain. The prevalence of HP is higher than recognized, especially its chronic form. Mechanisms of disease are still incompletely known. Strategies to improve detection and diagnosis are needed, and treatment options, principally avoidance, are limited. A workshop recommended: a population-based study to more accurately document the incidence and prevalence of HP; better classification of disease stages, including natural history; evaluation of diagnostic tests and biomarkers used to detect disease; better correlation of computerized tomography lung imaging and pathologic changes; more study of inflammatory and immune mechanisms; and improvement of animal models that are more relevant for human disease.

Interstitial lung diseases: characteristics at diagnosis and mortality risk assessment.

As the diagnostic assessment of the different forms of interstitial lung disease (ILD) is similar, this study aims to compare age, sex, the functional and broncho-alveolar lavage fluid (BALF) findings at diagnosis between the different forms of ILDs. In addition we want to determine which of these variables determine survival. We evaluated 315 patients (176 males and 139 females) in whom the diagnosis was made of sarcoidosis (n = 87), ILD due to connective tissue disease (n = 56), hypersensitivity pneumonitis (n = 50), idiopathic pulmonary fibrosis (IPF) (n = 64), other forms of idiopathic interstitial pneumonia (n = 29) or ILD due to an undefined form of fibrosis (n = 29). We analysed the role on outcome of type of disease, gender, age at diagnosis, type of cells in BALF, FVC and DLCO. In a Kaplan-Meier analysis IPF has the worst outcome in comparison with other types of ILDs. A Cox regression analysis showed that type of ILD, FVC, age at diagnosis and % of macrophages in BALF predict outcome of patients affected by ILD.

Occupational lung disease. Part 2. Discovering the cause of diffuse parenchymal lung disease.

Diffuse parenchymal lung disease (also known as interstitial lung disease) and acute irritant reactions are much less commonly managed by primary care physicians than asthma. Acute irritant reactions are typically readily recognized because of the immediate exposure-response relationship. As with asthma, a diagnosis of diffuse parenchymal lung disease should prompt a careful review of the patient's work history. Findings from history taking and radiography provide most of the data needed to establish a diagnosis of asbestosis or silicosis. A pulmonologist should be consulted about lung disease that eludes diagnosis. In cases in which a link between work and illness is strongly suspected, an occupational medicine specialist may be consulted for assistance with preparing reports for a workers' compensation claim as well as characterizing and quantifying impairment. Various government agencies provide extensive information about specific toxic exposures and occupational lung diseases by telephone and on the World Wide Web.

An outbreak of hypersensitivity pneumonitis at a metalworking plant: a longitudinal assessment of intervention effectiveness.

The authors describe a longitudinal assessment of intervention effectiveness in response to an outbreak of hypersensitivity pneumonitis (HP) at a metalworking facility. Thirty-five (29%) of the plant's 120 production workers were given a clinical diagnosis of HP during the two years of the investigation. Although quantitative exposure assessment tools were of limited utility, the investigators successfully used qualitative observations and the patients' return-to-work experiences to iteratively evaluate their exposure control recommendations. Recommended interventions included improving metalworking fluid management practices, enclosing selected metalworking fluid machining operations, eliminating mist cooling, exhausting two additional water-based industrial processes, increasing general dilution ventilation, and worker training. As of November 1999, 26 months into the outbreak, 51 percent (18) of the employees with a clinical diagnosis of hypersensitivity pneumonitis had been able to return to work. The symptom onset of the 35 workers who were given a clinical diagnosis of hypersensitivity pneumonitis during the two-year study period predated the implementation of the interventions. The collaboration of a multidisciplinary team appears to have allowed for successful intervention in this setting. A specific etiological agent(s) associated with the outbreak was not confirmed during the investigation. An acid fast isolate identified as being in the Mycobacterium chelonae group was detected in only one of the submitted metalworking fluid (MWF) sump samples. Longitudinally, there was a statistically significant difference in MWF sump bacteria (X(2) = 286.4, df = 17, p <.0001) and MWF sump fungi (X(2) = 28.1, df = 7, p <.0002). Measured oil mist air levels did not exceed the Occupational Safety and Health Administration's (OSHA's) permissible exposure limit (PEL), and in fact, did not exceed 0.5 mg/m(3).

Studies on the role of fungi in Sick Building Syndrome.

Sick Building Syndrome is a term used to describe symptoms in humans which result from problems with indoor air quality. Common complaints include dyspnea, flu-like symptoms, watering eyes, and allergic rhinitis. Although there is likely no single cause for Sick Building Syndrome, fungal contamination in buildings has increasingly been associated with this spectrum of symptoms. The authors describe 2 case studies, and other experimentation, that have investigated the role of fungi in the occurrence of Sick Building Syndrome.

[Principles of work capacity assessment in occupational respiratory diseases]. / Zasady orzekania o zdolnosci do pracy w chorobach zawodowych ukladu oddechowego.

Pneumoconiosis, occupational asthma, extrinsic allergic alveolitis and chronic bronchitis are the major problems among occupational respiratory diseases. The assessment of work capacity in these cases is based on the three criteria: (a) clinical and radiological symptoms and signs which determine the degree of the disease intensity; (b) the kind and degree of the lung function disturbances caused by these diseases; and (c) limitations resulting from prophylactic contraindications. There are numerous functional tests showing disturbances of the lung function. Simple spirometry should be performed as a necessary minimum. While assessing physical work capacity, the measurement of the maximum oxygen consumption is most essential.