A 46-year-old male was treated with corticosteroids for nonspecific interstitial pneumonia (NSIP). He was referred to our hospital and admitted for worsening dyspnea and diffuse ground-glass opacity on chest computed tomography (CT) during corticosteroid treatment. Gottron\'s sign was observed, and the patient was diagnosed with clinically amyopathic dermatomyositis on skin biopsy. We increased the corticosteroid dose and added immunosuppressive agents; however, the opacity on the chest CT worsened. Based on periodic-acid-Schiff-positive granular material in the bronchoalveolar lavage fluid and the presence of anti-GM-CSF antibodies, the patient was diagnosed with autoimmune pulmonary alveolar proteinosis (APAP). The concentration of anti-GM-CSF antibodies in preserved serum was also elevated when the patient was diagnosed with NSIP. Thus, we assumed that NSIP and APAP coexisted, and that APAP manifested during immunosuppressive therapy. When exacerbation is observed during the treatment of interstitial pneumonia with immunosuppressive agents, it is necessary to consider APAP.

Interstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases.

Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist\'s aim is to recognize the pathologic-morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical-therapeutic management of the patient.

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. Here, we investigated whether single nucleotide variants susceptible to idiopathic pulmonary fibrosis might be associated with interstitial lung disease or AD in Japanese RA patients. Genotyping of rs2736100 [C/A] in TERT and rs1278769 [G/A] in ATP11A was conducted in 98 RA patients with usual interstitial pneumonia, 120 with nonspecific interstitial pneumonia (NSIP), 227 with AD, and 422 without chronic lung disease using TaqMan assays. An association with AD in RA was found for rs2736100 (p = 0.0043, Pc = 0.0129, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11-1.77). ATP11A rs1278769 was significantly associated with NSIP in older RA patients (>65 years, p = 0.0010, OR 2.15, 95% CI 1.35-3.40). This study first reported an association of rs2736100 with AD in RA patients and ATP11A rs1278769 with NSIP in older RA patients.

A 58-year-old woman with cough and dyspnea who was suspected of having idiopathic interstitial pneumonia had been treated with corticosteroids and cyclosporine, but the symptoms had worsened. There were no findings to suspect pulmonary alveolar proteinosis (PAP) in the bronchoalveolar lavage fluid, 17 months after the start of treatment. The transbronchial lung biopsy specimens showed eosinophilic bodies that strongly stained with periodic acid-Schiff staining. Anti-granulocyte macrophage colony-stimulating factor (anti-GM-CSF) antibodies were detected in her serum. We diagnosed the patient with autoimmune PAP. Thus, we present a rare case of PAP presenting atypical radiological images and bronchoalveolar lavage fluid findings.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease. Although high-resolution computed tomography (HRCT) is important for the diagnosis of IPF, the changes in the HRCT findings in IPF are not fully understood. The patient was a 66-year-old man. His HRCT findings had atypically developed from a probable usual interstitial pneumonia pattern to a nonspecific interstitial pneumonia (NSIP) like pattern over 6 years. On the basis of the histologic examination and multidisciplinary discussion, IPF was diagnosed, and nintedanib, administered. This case can be useful for the differential diagnosis of IPF and NSIP.

BACKGROUND: Anti-synthetase syndrome (ASSD) is a chronic autoimmune condition characterized by antibodies directed against an aminoacycl transfer RNA synthetase (ARS) along with a group of clinical features including the classical clinical triad: inflammatory myopathy, arthritis, and interstitial lung disease (ILD). ASSD is highly heterogenous due to different organ involvement, and ILD is the main cause of mortality and function loss, which presents as different patterns when diagnosed. We designed this retrospective cohort to describe the clinical features and disease behaviour of ASSD associated ILD.
METHODS: Data of 108 cases of ASSD associated ILD were retrospectively collected in Beijing Chaoyang Hospital from December 2017 to March 2019. Data were obtained from the Electronic Medical Record system. Patients were divided into 5 groups according to distinct aminoacyl tRNA synthetase (ARS) antibodies.
RESULTS: Overall, 108 consecutive patients were recruited. 33 were JO-1 positive, 30 were PL-7 positive, 23 were EJ positive, 13 were PL-12 positive and 9 were OJ positive. The JO-1 (+) group had a significant higher rate of mechanic\'s hand (57.6%) than other 4 groups. Polymyositis/dermatomyositis (PM/DM) was diagnosed in 25 (23.1%) patients and no difference was observed among the 5 groups. The PL-7 (+) group had a higher frequency of UIP pattern (13.3%) than the other 4 groups but the difference was not significant, and the EJ (+) group had the most frequent OP pattern (78.2%), which was significantly higher than the PL-7 (+) (P < 0.001) and PL-12 (+) groups (P = 0.025). The median follow-up time was 10.7 months, during which no patients died. All received prednisone treatment, with or without immunosuppressants. At the 6-month follow-up, 96.3% of all patients (104/108) had a positive response to therapy, the JO-1 (+) and EJ (+) groups had a significantly higher improvement of forced vital capacity than the other 3 groups (P < 0.05), and the PL-7 group had the lowest FVC improvement (P < 0.05). The JO-1 (+) group and EJ (+) group had significantly higher anti-Ro-52 positive occurrence than the other 3 groups (P < 0.05).
CONCLUSIONS: Anti PL-7 antibody had the same frequency as anti-JO-1 in ASSD-ILD, in which the ILD pattern was different with distinct anti-ARS antibodies. Most ASSD-ILD had a positive response to steroid therapies, with or without immunosuppressants. The PL-7 (+) group had the highest occurrence of UIP pattern, and a significantly lower response to therapy.

Nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP) are major subtypes of idiopathic interstitial pneumonias (IIPs) and closely related to connective tissue diseases (CTDs). \"NSIP with OP overlap\" is a controversial finding that has recently appeared in the criteria of interstitial pneumonia with autoimmune features (IPAF). However, details of this controversial entity are not well known.
To determine the frequency of \"NSIP with OP overlap\" pattern in IIPs and to identify differences from idiopathic NSIP (iNSIP).
In 524 patients with interstitial pneumonia from 39 institutes who underwent surgical lung biopsy, 444 were diagnosed as IIPs by a multidisciplinary discussion meeting via a cloud-based integrated database. Among these patients, 44 (9.9%) who had iNSIP and 21 (4.7%) with histopathologically-defined \"NSIP with OP overlap\" pattern (a pathological NSIP and OP pattern, but without a UIP pattern) were retrospectively studied.
Patients with \"NSIP with OP overlap\" pattern showed a significantly greater extent of consolidation (p < 0.001), more subpleural ground glass attenuation (p = 0.036), and more peripheral + bronchovascular distribution (p = 0.009) on high-resolution computed tomography than those with iNSIP. The incidences of newly-developed CTDs during follow-up was similar between the groups and polymyositis/dermatomyositis was the most frequent CTD in both groups. Nearly half of the patients fulfilled IPAF criteria, but no significant difference was found between iNSIP and \"NSIP with OP overlap\" pattern (47.7% vs. 42.9, p = 0.712). The incidence of acute exacerbation and the survival rates were similar between the groups.
The incidence of \"NSIP with OP overlap\" pattern is 4.7% in IIPs. The frequency of newly-developed CTDs during follow-up, mainly polymyositis/dermatomyositis, the frequency of acute exacerbation, and the survival rate in \"NSIP with OP overlap\" pattern are similar to those of iNSIP.

BACKGROUND: Pirfenidone treatment can slow decline in forced vital capacity (FVC) in idiopathic pulmonary fibrosis (IPF). However, its effects for usual interstitial pneumonia (UIP) with pleuroparenchymal fibroelastosis-like lesions (UIP+PPFELL) and UIP with nonspecific interstitial pneumonia (UIP+NSIP) are unclear.
OBJECTIVE: The aim of study is to assess pirfenidone effectiveness for UIP+PPFELL and UIP+NSIP.
METHODS: We retrospectively analysed data from 58 IPF patients treated with pirfenidone more than 6 months. The outcomes of interest were 6-month follow-up pulmonary function test results, progression-free survival (PFS) and overall survival (OS). Treatment was considered effective if FVC decline was <5% during the 6-month period. We compared clinical characteristics, effectiveness, PFS and OS between patients with typical IPF (n = 32), UIP+PPFELL (n = 12) and UIP+NSIP (n = 14).
RESULTS: Data from 58 IPF patients were analysed. At the 6-month follow-up examination, treatment was deemed effective for 9 of 14 (64%) UIP+NSIP patients, 6 of 12 (50%) UIP+PPFELL patients and 14 of 32 (44%) patients with typical IPF. The 6-month decline in FVC before treatment was greater than that after starting treatment in the UIP+NSIP (-210 vs. -57 mL; P = 0.09), UIP+PPFELL (-370 vs. -89 mL; P = 0.001) and typical IPF (-172 vs. -85 mL; P = 0.37). PFS did not significantly differ between the three groups. OS was significantly shorter for UIP+PPFELL (312 days) than for UIP+NSIP (545 days) and typical IPF (661 days).
CONCLUSIONS: Pirfenidone decreased the decline in FVC in patients with UIP+PPFELL and UIP+NSIP, as well as in those with typical IPF. However, outcomes were worse for patients with UIP+PPFELL.

BACKGROUND: Although increasing data supports the use of transbronchial lung cryobiopsies (TBLCs) for the diagnosis of diffuse parenchymal lung diseases (DPLDs), its role as an alternative to surgical lung biopsy (SLB) is still under debate. The aim of this study was to assess the benefit of additional SLBs performed in selected patients after TBLCs.
METHODS: We conducted a multicentric Belgian prospective trial in which SLBs were performed after TBLCs when the pathological diagnosis was uncertain or if a nonspecific interstitial pneumonia (NSIP) pattern was observed hypothesizing that SLB could provide additional information and that a co-existent UIP pattern could be missed.
RESULTS: Eighty-one patients with TBLCs performed for a DPLD were included in the study between April 2015 and December 2019. A specific histological diagnosis was obtained in 52 patients (64%) whereas no pathological diagnosis following TBLCs was obtained in 13 patients (16%) and a pattern suggestive of a NSIP was observed in 16 patients (20%). Fourteen out of these 29 patients had SLBs after TBLCs. SLBs showed a UIP pattern in 11 (79%), a pattern suggestive of a hypersensitivity pneumonitis in two (14%) and a NSIP pattern in one patient (7%). Among the 16 patients with pathological NSIP following TBLCs, six underwent a SLBs showing a UIP in five and confirming a NSIP in one patient only. A retrospective pathological analysis of patients having both procedures showed a lower diagnostic confidence and agreement among pathologists for TBLCs compared to SLBs. Major factors underlying the added value of SLBs were the bigger size of the sample as well as the subpleural localization of the biopsies.
CONCLUSIONS: TBLCs are useful in the setting of DPLDs with a good diagnostic yield. However, our study suggests that SLB provides critical additional information in case TBLCs are inconclusive or show a pattern suggestive of a NSIP, questioning the accuracy of TBLC to adequately identify this histological pattern.