Natural history of indolent-anti-synthetase syndrome-associated interstitial lung disease.

BACKGROUND: Anti-synthetase syndrome-associated interstitial lung disease (ASS-ILD) may occur without myositis. Although a recent Japanese guide proposed a watch-and-wait approach for chronic ASS-ILD without obvious progression, the natural history of this subgroup and the appropriateness of the watch-and-wait approach remain unclear. We aimed to describe the natural history of ASS-ILD, that is sufficiently indolent to be a candidate for the watch-and-wait approach. METHODS: Among consecutive patients with ASS-ILD, we retrospectively identified those without myositis, acute/subacute onset, and significant lung function impairment, which qualified them as indolent-ASS-ILD cases, and described their natural course. Additionally, we evaluated the risk factors for fibrosis progression on computed tomography (CT) using the Cox proportional hazards model. RESULTS: Among 80 patients with ASS-ILD, we identified 33 with indolent-ASS-ILD, all of whom were initially followed up with a watch-and-wait approach. Among 30 patients with sufficient follow-up data, 27 (90%) showed a stable course without treatment over 24 months. Subsequently, four patients experienced ≥10% relative forced vital capacity (FVC) decline without treatment during a median follow-up duration of 81 months. Seven patients showed fibrosis progression with >10% increase in the total lung area on CT. Higher levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) were associated with fibrosis progression on CT. CONCLUSION: Most patients with indolent-ASS-ILD did not experience ≥10% relative FVC decline over five years without treatment. However, fibrosis progression on CT, which seemed to precede significant FVC decline, occurred more frequently, especially in patients with higher KL-6 and SP-D levels.

Cryptogenic organizing pneumonia: clinical outcomes of 60 consecutive cases.

Background: Cryptogenic organizing pneumonia (COP) improves rapidly following corticosteroid treatment; however, relapse is common. Therefore, this retrospective observational study aimed to clarify the clinical outcomes of COP and identify the predictive factors for relapse. Methods: The laboratory findings, pulmonary function test results, computed tomography (CT) findings, and clinical outcomes of 60 consecutive COP patients treated at our institution between 2007 and 2013 were retrospectively reviewed. The clinical characteristics of COP patients who did and did not show improvement were compared to identify the predictive factors for relapse in patients showing improvement. Results: Forty-one patients showed improvement without relapsing (Group 1), whereas thirteen relapsed after showing improvement (Group 2). Six patients did not show any improvement (Group 3). The serum Krebs von den Lungen-6 (KL-6) levels in Group 3 were greater than those in Groups 1 and 2 (P=0.004). The incidence of traction bronchiectasis and reticular opacities in Group 3 was higher than that in Groups 1 and 2 (P=0.048 and P=0.006, respectively). The cut-off levels of C-reactive protein (CRP), blood neutrophil fraction (%neutrophils) and lymphocyte fraction (%lymphocytes) for predicting relapse were 6.84 mg/dL, 68.7% and 14.1% in Groups 1 and 2, respectively. The log-rank test revealed that high serum CRP levels (P<0.001), high %neutrophils (P=0.003) and low %lymphocytes (P=0.006) showed significant correlations with a shorter time to the first relapse episode. Conclusions: Chest CT findings depicting pulmonary fibrosis and high serum KL-6 levels were correlated with the non-improvement of COP. Blood test results indicating inflammatory reactions were correlated with relapse in patients with COP showing improvement.

Neutrophil-to-Lymphocyte Ratio in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

BACKGROUND: This study aimed to clarify the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). METHODS: Eighty-six patients diagnosed with AE-IPF were included in this single-center retrospective study. The NLR was calculated by dividing the peripheral neutrophil count by the peripheral lymphocyte count. The cut-off values of the NLR for predicting 90-day survival were determined using receiver operating characteristic curve analysis. Oxygenation deterioration on days 4 and 8 relative to that on day 1 was clinically defined. The prognostic value of NLR was evaluated using Cox proportional hazard regression analysis. RESULTS: The cut-off value of day-1, day-4, and day-8 NLRs for predicting 90-day survival was 12.13, 14.90, and 10.56, respectively. A higher day-1 NLR was a significant predictor of a poor prognosis in univariate and multivariate analyses. Survival was significantly better in patients without oxygenation deterioration on days 4 and 8 than in those with deterioration. Day-4 and day-8 NLR could predict 90-day survival in patients without oxygenation deterioration. CONCLUSIONS: Day-1 NLR was a useful predictor of 90-day survival in AE-IPF. Further, monitoring day-4 and day-8 NLRs and evaluating oxygenation deterioration may be useful for managing AE-IPF.

A Case of Lymphangioleiomyomatosis Showing the Development of Mycobacterium abscessus subsp. massiliense Infection During Sirolimus Therapy.

Among nontuberculous mycobacterial pulmonary diseases (NTM-PDs), Mycobacterium abscessus species pulmonary disease (MABS-PD) is one of the most severe and intractable infections. We herein report a 45-year-old woman with advanced lymphangioleiomyomatosis (LAM) who developed MABS-PD while undergoing sirolimus therapy. MABS-PD was immediately controlled using antibiotic therapy, although the patient's lung transplant registration was significantly delayed. To our knowledge, this is the first case report on the development of NTM-PD in a patient with LAM before lung transplantation. This case suggests that the early diagnosis and optimal treatment of NTM-PD are crucial in patients with advanced LAM.

Autoimmune Pulmonary Alveolar Proteinosis Complicated by Myelodysplastic Syndrome: A Case Report.

Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal surfactant accumulation in peripheral air spaces. Autoimmune PAP (APAP) results from macrophage dysfunction caused by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, and the presence of antibodies more than the cutoff value is specific for APAP. In contrast, secondary PAP (SPAP) does not require anti-GM-CSF autoantibodies and is complicated by other diseases, including myelodysplastic syndrome (MDS). A 73-year-old man with anemia and thrombocytopenia was diagnosed with APAP and MDS simultaneously. The measurement of serum anti-GM-CSF autoantibodies is important for the correct diagnosis and management of PAP, even with an established diagnosis of underlying SPAP-suggestive disease.

COVID-19 in Patients with Pre-Existing Interstitial Lung Disease: Potential Value of a Steroid-Based Treatment Strategy.

The prognosis of patients with coronavirus disease 2019 (COVID-19) and pre-existing interstitial lung disease (preILD) is poor, and no effective treatment strategy has been determined. The aim of this study was to assess the effectiveness of a steroid-based treatment strategy for patients with COVID-19 and preILD. We retrospectively reviewed the medical records of 610 consecutive patients with COVID-19 treated at our institution between 1 March 2020 and 30 October 2021 and identified 7 patients with preILD, all of whom were treated with corticosteroids and remdesivir. All the patients were men with a median age of 63 years. Three of four patients with severe disease required invasive positive-pressure ventilation (n = 2) or nasal high-flow therapy (n = 1). All three patients could be weaned from respiratory support; however, one died in hospital. The remaining patient with severe COVID-19 had a do-not-resuscitate order in place and died while hospitalized. All three patients with moderate COVID-19 were discharged. The 30-day mortality was 0%, and the mortality rate during the entire observation period was 28.5%. The prognosis of our patients with COVID-19 and preILD has been better than in previous reports. Our management strategy using corticosteroids may have improved these patients' prognosis.

Vocal cord paralysis associated with pleuroparenchymal fibroelastosis: A case report and literature review.

Here, we report a case of idiopathic pleuroparenchymal fibroelastosis (PPFE) that progressed to pulmonary aspergilloma, aspiration pneumonia, and left vocal cord paralysis (VCP). To date, five cases of PPFE with VCP have been reported, including the present case. Aspiration pneumonia occurred in three cases, leading to death in two cases. Four cases had left-sided paralysis, in two of which, the paralysis occurred on side opposite to the predominant side (right side) of PPFE. Structural mechanisms underlying the recurrent laryngeal nerve could be involved. This report may further highlight the existence of hoarseness and dysphagia in PPFE.

Left Vocal Cord Paralysis in Idiopathic Pleuroparenchymal Fibroelastosis: A Case Report.

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease that is characterized by predominant upper lobe fibrosis and pleural thickening. In this report, we present an unusual case of idiopathic PPFE with left vocal cord paralysis that developed repeated aspiration pneumonia. Vocal cord paralysis is a rare complication of PPFE, and two mechanisms can be proposed: 1) Fibrous adhesion of the recurrent laryngeal nerve to the chest wall can cause stretching of the nerve. 2) Traction or compression of the recurrent laryngeal nerve due to the distortion of the tracheobronchial tree can cause paralysis of the vocal cord. Finally, to reduce the risk of aspiration pneumonia, laryngoscopic evaluation of the vocal cord is recommended in patients with PPFE with hoarseness and dysphagia for early intervention.

Autoimmune Pulmonary Alveolar Proteinosis That Improved after a COVID-19 Episode.

Autoimmune pulmonary alveolar proteinosis (APAP) is caused by macrophage dysfunction owing to the presence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies. A 77-year-old man with APAP was referred to our hospital for whole-lung lavage (WLL) due to oxygenation exacerbation and pulmonary shadows. The patient had had coronavirus disease 2019 (COVID-19) during the APAP evaluation before WLL. About three months after COVID-19 resolved, his oxygenation and shadow reflecting APAP had obviously improved, thus avoiding the need for WLL. We suspected that the improvement in APAP was due to various immunological reactions induced by COVID-19.

Poor Outcome and Mortality in Patients with Lower Lung-Dominant Sarcoidosis.

Background: Pulmonary sarcoidosis predominantly affects the upper lung zones but sometimes affects the lower lung zones. We hypothesised that patients with lower lung zone-dominant sarcoidosis had lower baseline forced vital capacity, progressive restrictive lung function decline, and higher long-term mortality. Methods: We retrospectively reviewed clinical data including the pulmonary function tests of 108 consecutive patients with pulmonary sarcoidosis pathologically confirmed by lung and/or mediastinal lymph node biopsy from 2004 to 2014 from our database. Results: Eleven patients (10.2%) with lower lung zone-dominant sarcoidosis were compared with 97 patients with nonlower lung zone-dominant sarcoidosis. The median age of the patients with lower dominance was significantly older (71 vs. 56, p = 0.0005). The patient with lower dominance had a significantly lower baseline percent forced vital capacity (FVC) (96.0% vs. 103%, p = 0.022). The annual change in FVC was -112 mL in those with lower dominance vs. 0 mL in nonlower dominance (p = 0.0033). Fatal acute deterioration was observed in three patients (27%) in the lower dominant group. Overall survival in the lower dominant group was significantly worse. Conclusions: Patients with lower lung zone-dominant sarcoidosis had an older age and lower baseline FVC with disease progression and acute deterioration associated with higher long-term mortality.

Cases of severe Mycobacterium avium lung disease occurred in a married couple caused by identical strain.

Bacteria of the Mycobacterium avium complex, which are environmental organisms found in soil and water, have been found to cause human lung diseases. Although infection is reported to occur in cohabiting patients, the incidence of infection from the single clone remains rarely documented. Herein, we report a case of M. avium lung disease caused by specimens with the same clone strains in a married couple. The wife, a 67-year-old female, had severe M. avium lung disease despite receiving multidrug chemotherapy for eleven years. The husband, a 68-year-old male, died of acute lung injury complicated by M. avium pleurisy. The result of the variable-number tandem-repeat analysis of isolates from serial sputum specimens of both patients indicated that the severe M. avium lung disease in a married couple was caused by the isolates with identical pattern. This case were considered to have acquired clarithromycin resistance during each clinical course, revealing the possibility of infection with a strain that may induce severe pulmonary condition.

Interleukin-11 in idiopathic pulmonary fibrosis: predictive value of prognosis and acute exacerbation.

Background: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with a poor prognosis and unknown aetiology. We have recently clarified the prognostic value of the serum platelet-derived growth factor (PDGF) level in patients with IPF. Interleukin (IL)-11 is a member of the IL-6 family, and in vivo and in vitro studies have suggested that it has profibrotic effects in pulmonary fibrosis. In this study, we investigated the predictive value of the serum IL-11 level in patients with IPF for survival and occurrence of acute exacerbation (AE). Methods: This retrospective study included 68 patients with IPF diagnosed according to the 2018 guideline. Serum PDGF levels were measured using the Bio-Plex method and serum IL-11 levels using enzyme-linked immune-sorbent assay. Cytokine production per lung volume was evaluated using the serum cytokine/percent predicted forced vital capacity (%FVC) value. Results: Forty-six patients were male and the median age was 67 years. The serum IL-11/%FVC value was significantly correlated with the percent predicted diffusing capacity of carbon monoxide (ρ=-0.518, P<0.001) and modified Medical Research Council score for shortness of breath (mMRC) (ρ=0.335, P=0.006) by Spearman's rank correlation analysis. Multivariate Cox proportional hazard regression analysis revealed that the serum IL-11/%FVC value was a significant prognostic factor after adjustment for the serum PDGF/%FVC value and other clinical parameters including mMRC and lymphocyte percentage in bronchoalveolar lavage [hazard ratio (HR): 88.540, 95% confidence interval (CI): 1.905-4,115.686, P=0.022]. IL-11/%FVC value was also a significant predictor of AE after adjustment for age and PDGF/%FVC (HR: 1,815.443, 95% CI: 10.49-314,109.219, P=0.004). Conclusions: The serum IL-11/%FVC value was an independent predictor of prognosis and AE occurrence in patients with IPF, and the IL-11 level appeared to show pathophysiologic value in IPF.

Immune Checkpoint Inhibitor-Related Pneumonitis in Lung Cancer Patients with Interstitial Lung Disease: Significance of Radiological Pleuroparenchymal Fibroelastosis.

INTRODUCTION: Pleuroparenchymal fibroelastosis (PPFE) findings are associated with poor prognosis in interstitial lung disease (ILD). However, the effect of PPFE findings on the development of immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis), a life-threatening adverse event, in lung cancer patients with ILD has not been elucidated. We aimed to determine whether PPFE findings are a risk factor for ICI-pneumonitis in lung cancer patients with ILD. METHODS: We retrospectively examined 712 lung cancer patients, including 173 patients with background ILDs, who received ICI therapy in our institute between December 2015 and May 2021. Background ILDs were radiologically classified into three types: lone PPFE, other ILDs with PPFE, and other ILDs without PPFE. The cumulative ICI-pneumonitis incidence curves and median overall survival (mOS) were compared between the three radiological types, and risk factors for ICI-pneumonitis were evaluated. RESULTS: Of 173 eligible patients with ILD, 23 patients (13.3%) experienced ICI-pneumonitis. The Kaplan-Meier method and the log-rank test showed that lone PPFE patients had significantly lower incidence of ICI-pneumonitis (p = 0.024) and longer mOS (575 vs. 326 days; p = 0.0096) than other ILDs patients. ICI-pneumonitis (p = 0.35) and mOS (p = 0.29) were not significantly different between other ILDs with and without PPFE. A multivariate Cox proportional hazards regression analysis revealed that lone PPFE pattern was an independent predictive factor for ICI-pneumonitis (hazard ratio, 0.20; 95% confidence interval, 0.043-0.93; p = 0.040). CONCLUSION: ICI therapy could be safer in lone PPFE patients than in other ILDs patients with lung cancer.

Design and rationale of the Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry.

BACKGROUND: Numerous studies investigated patients with IPF; however, only a few examined patients with idiopathic interstitial pneumonias (IIPs). METHODS: The Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry, which was initiated in December 2016, is a multicenter prospective observational study of patients newly diagnosed with IIPs from 86 facilities treating ILDs. The plan is to enroll more than 600 new patients during the 2-year enrolment period and to follow their progress for 3 years after the last case enrolment. If additional consent is obtained, the study will continue for another 2 years. Research questions mainly focus on identifying the frequency by IIP classification, patient background, and diagnostic methods during enrolment, survival, acute exacerbation rate, changes in high-resolution CT imaging, forced vital capacity, and interstitial pneumonia markers over time. Other research questions, including those regarding disease behavior in patients with progressive fibrosing-ILD and new biomarkers associated with genetic predispositions, will be investigated. DISCUSSION: The JIPS Registry will provide a comprehensive description of the disease progression, prognosis, treatment status, new biomarkers, and validity of guidelines and central multidisciplinary decisions for IPF and similar diseases that can be differentiated from IPF among IIPs. ETHICS AND DISSEMINATION: Ethical approval was obtained from the institutional review board of Kanagawa Cardiovascular and Respiratory Center (KCRC-16-0005), and that of Jichi Medical University approved the biobank part (I18-005). Results will be published in peer-reviewed journals and will be presented at national and international conferences. TRIAL REGISTRATION: ClinTrials.gov Registry (NCT03041623, first posted on February 3, 2017).

Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation.

BACKGROUND: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. METHODS: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from -1,000 to 0 HU. RESULTS: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from -1,000 to -857 and -143 to 0 HU. CONCLUSION: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

Fibrotic Hypersensitivity Pneumonitis Diagnosed by a Re-evaluation with Bronchoalveolar Lavage at Disease Deterioration.

A 79-year-old man was admitted with worsening cough, dyspnea, and increased ground-glass opacity on chest computed tomography (CT). He had been diagnosed with idiopathic pulmonary fibrosis given the absence of an identifiable cause of interstitial pneumonia, chest CT findings, and absence of lymphocytosis in bronchoalveolar lavage (BAL) fluid. Meticulous history taking revealed extensive exposure to inciting antigens contained in chicken fertilizer before symptom worsening. A re-evaluation with BAL showed lymphocytosis, and clinical improvement with antigen avoidance confirmed the diagnosis of fibrotic hypersensitivity pneumonitis (fHP). A re-evaluation with BAL at disease deterioration after possible exposure to inciting antigen can facilitate a correct fHP diagnosis.

Predictive factors for relapse in corticosteroid-treated patients with chronic eosinophilic pneumonia.

Background: Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterised by an abnormal and marked accumulation of eosinophils in the interstitium and alveolar spaces of the lungs. Systemic corticosteroid (CS) therapy leads to marked improvement. However, relapse is common in the clinical course, and the predictive factors for relapse of CEP are not well known. This study aimed to investigate predictive factors for relapse in CS-treated cases of CEP. Methods: We identified consecutive patients with CEP at our institution between 1999 and 2019. We retrospectively reviewed 36 CS-treated patients with CEP who underwent bronchoalveolar lavage (BAL) and high-resolution computed tomography (CT) at diagnosis. We examined relapse at least 1 year after the initiation of CS treatment. Statistical analysis included univariate and multivariate Cox proportional hazard regression analyses; P<0.05 was considered statistically significant. Results: The median (interquartile range) age at diagnosis was 59.5 years (47.8-70.0 years). This study included 13 men and 23 women. Twenty-five patients (69.4%) were never smokers and 15 (41.7%) had asthma. The peripheral blood eosinophil percentage was 35.0% (15.6-55.8%), and the BAL eosinophil percentage was 40.8% (10.7-68.5%). The median serum surfactant protein-D (SP-D) level was 135 ng/mL (82.2-176.7 ng/mL). High-resolution CT revealed centrilobular opacities in 23 patients (63.9%). Relapse of CEP was observed in 20 patients (55.6%). Higher serum SP-D levels and the presence of centrilobular opacities on high-resolution CT were significant predictors of relapse in multivariate Cox proportional hazard regression analysis (P=0.017 and P=0.028, respectively). Additionally, we devised a relapse prediction model for CS-treated CEP using two categorical parameters: the presence of centrilobular opacities and serum levels of SP-D (>135/≤135 ng/mL). Based on these parameters, cases were scored 2, 1, or 0. Patients with a score of 2 experienced relapses earlier than those with scores of 1 and 0 (log-rank test; P=0.006, P=0.003, respectively). Conclusions: Centrilobular opacities on high-resolution CT and higher serum SP-D levels at diagnosis may be predictive factors for relapse in CS-treated patients with CEP.

Two cases of nintedanib-induced diarrhoea treated using a 5-hydroxytryptamine type 3 receptor antagonist.

Nintedanib-induced diarrhoea may be controlled by ramosetron by modulation of intestinal motility as for irritable bowel syndrome #pulmonaryfibrosis https://bit.ly/3OQVAII.