No abstract

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax. Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions. Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure. Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability. Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality. Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

A glutamic acid at residue 69(Glu69) in the HLA-DPB1 gene (Glu69) is associated with chronic beryllium disease (CBD) and possibly beryllium sensitization (BeS). This study tested the hypothesis that MHC class II polymorphisms are important in susceptibility to BeS and CBD and that the Glu69 variant is related to markers of disease severity. Genomic DNA was obtained from BeS (n = 50), CBD (n = 104), and beryllium-exposed nondiseased (Be-nondiseased) (n = 125) subjects. HLA-DPB1, -DRB1, and -DQB1 genotypes were determined by (sequence-specific primers) PCR. Disease severity was assessed by pulmonary function and exercise testing. A higher frequency of the DPB1 Glu69 gene was found in CBD and BeS compared with the Be-nondiseased subjects, with odds ratios of 10.1 for CBD vs Be-nondiseased and 9.5 for BeS vs Be-nondiseased. The majority of BeS and CBD subjects displayed non-0201 Glu69 alleles. Glu69 homozygosity was higher in the CBD subjects, while BeS subjects were intermediate and Be-nondiseased lowest. DRB1*01 and DQB1*05 phenotypes were reduced in CBD vs Be-nondiseased subjects, while DRB1*13 and DQB1*06 were associated with CBD in the absence of Glu69. Markers of disease severity, including a lower forced vital capacity, diffusion capacity for carbon monoxide, PaO2 at rest, maximum workload on exercise testing, and a higher arterial-alveolar gradient at rest, were associated with Glu69 homozygosity. We conclude that DPB1 Glu69 is a marker of sensitization and not specific for disease. Glu69 homozygosity acts as a functional marker associated with markers of CBD severity.

The blood beryllium lymphocyte proliferation test is used in medical surveillance to identify both beryllium sensitization and chronic beryllium disease. Approximately 50% of individuals with beryllium sensitization have chronic beryllium disease at the time of their initial clinical evaluation; however, the rate of progression from beryllium sensitization to chronic beryllium disease is unknown. We monitored a cohort of beryllium-sensitized patients at 2-year intervals, using bronchoalveolar lavage and repeated transbronchial lung biopsies to determine progression to chronic beryllium disease as evidenced by granulomatous inflammation in lung tissue. Fifty-five individuals with beryllium sensitization were monitored with a range of 2 to 5 clinical evaluations. Disease developed in 17 sensitized individuals (31%) within an average follow-up period of 3.8 years (range, 1.0-9.5 years). Thirty-eight of the 55 (69%) remained beryllium sensitized without disease after an average follow-up time of 4.8 years (range, 1.7-11.6 years). Progressors were more likely to have worked as machinists. We found no difference in average age, sex, race or ethnicity, smoking status, or beryllium exposure time between those who progressed to chronic beryllium disease and those who remained sensitized without disease. We conclude that beryllium sensitization is an adverse health effect in beryllium-exposed workers and merits medical follow-up.