Interstitial Lung Disease Subtypes Research Articles

Nintedanib for non-IPF progressive pulmonary fibrosis: 12-month outcome data from a real-world multicentre observational study.

Nintedanib slows lung function decline for patients with non-idiopathic pulmonary fibrosis progressive pulmonary fibrosis (PPF) in clinical trials, but the real-world safety and efficacy are not known. In this retrospective cohort study, standardised data were collected from patients in whom nintedanib was initiated for PPF between 2019 and 2020 through an early-access programme across eight centres in the United Kingdom. Rate of lung function change in the 12 months pre- and post-nintedanib initiation was the primary analysis. Symptoms, drug safety, tolerability and stratification by interstitial lung disease subtype and computed tomography pattern were secondary analyses. 126 patients were included; 67 (53%) females; mean±sd age 60±13 years. At initiation of nintedanib, mean forced vital capacity (FVC) was 1.87 L (58% predicted) and diffusing capacity of the lung for carbon monoxide (D LCO) was 32.7% predicted. 68% of patients were prescribed prednisolone (median dose 10 mg) and 69% were prescribed a steroid-sparing agent. In the 12 months after nintedanib initiation, lung function decline was significantly lower than in the preceding 12 months: FVC -88.8 mL versus -239.9 mL (p=0.004), and absolute decline in D LCO -2.1% versus -6.1% (p=0.004). Response to nintedanib was consistent in sensitivity and secondary analyses. 89 (71%) out of 126 patients reported side-effects, but 86 (80%) of the surviving 108 patients were still taking nintedanib at 12 months with patients reporting a reduced perception of symptom decline. There were no serious adverse events. In PPF, the real-world efficacy of nintedanib replicated that of clinical trials, significantly attenuating lung function decline. Despite the severity of disease, nintedanib was safe and well tolerated in this real-world multicentre study.

Idiopathic pleuroparenchymal fibroelastosis

The term idiopathic pleuroparenchymal fibroelastosis refers to a rare interstitial lung disease that predominantly involves the upper lobes. It has been considered a rare subtype of interstitial lung disease since 2013, when it was included in the joint consensus statement on the diagnosis of interstitial lung diseases published by the American Thoracic Society (ATS) and the European Respiratory Society (ERS).Currently, two distinct types of pleuroparenchymal fibroelastosis are recognized: the idiopathic type for cases in which it has not been possible to establish a specific etiology and a secondary type associated with a variety of different causes.The diagnosis of pleuroparenchymal fibroelastosis must be managed from a combined clinical and radiological perspective. High-resolution computed tomography (HRCT) is the imaging method of choice for the evaluation and diagnosis of pleuroparenchymal fibroelastosis. In many cases, the diagnosis will be based exclusively on the HRCT findings and histologic confirmation will be unnecessary.This article describes the clinical, radiological, and histological characteristics of pleuroparenchymal fibroelastosis, discussing the different associations with this entity and its differential diagnosis.

Fibroelastosis pleuroparenquimatosa idiopática (FEPPI)

The term idiopathic pleuroparenchymal fibroelastosis refers to a rare interstitial lung disease that predominantly involves the upper lobes. It has been considered a rare subtype of interstitial lung disease since 2013, when it was included in the joint consensus statement on the diagnosis of interstitial lung diseases published by the American Thoracic Society (ATS) and the European Respiratory Society (ERS).Currently, two distinct types of pleuroparenchymal fibroelastosis are recognized: the idiopathic type for cases in which it has not been possible to establish a specific etiology and a secondary type associated with a variety of different causes.The diagnosis of pleuroparenchymal fibroelastosis must be managed from a combined clinical and radiological perspective. High-resolution computed tomography (HRCT) is the imaging method of choice for the evaluation and diagnosis of pleuroparenchymal fibroelastosis. In many cases, the diagnosis will be based exclusively on the HRCT findings and histologic confirmation will be unnecessary.This article describes the clinical, radiological, and histological characteristics of pleuroparenchymal fibroelastosis, discussing the different associations with this entity and its differential diagnosis.

Imaging biomarkers of lung ventilation in interstitial lung disease from 129Xe and oxygen enhanced 1H MRI

PurposeTo compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. Study typeProspective longitudinal. PopulationForty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. Field strength/sequenceMRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. AssessmentFive 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. Statistical testTo evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. ResultsThe global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. Data conclusionNeither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.

Clinical Outcomes and Prognosis of Patients With Interstitial Lung Disease Undergoing Lung Cancer Surgery: A Propensity Score Matching Study

BackgroundPatients with interstitial lung disease (ILD) may have a poor prognosis after lung cancer surgery because of respiratory complications and increased recurrence rates due to limited resection. Few studies have investigated prognosis after surgery by matching clinical variables between patients with and without ILD. Patients and MethodsMedical records of patients who underwent lung cancer surgery between January 2010 and August 2020 at a referral hospital in South Korea were reviewed. Patients with ILD were identified based on preoperative computed tomography findings. Through propensity score matching, the clinical outcomes and prognoses of patients with (ILD group) and without ILD (control group) were compared. ResultsOf 1629 patients, 113 (6.9%) patients with ILD were identified, of whom 104 patients were matched. Before matching, patients with ILD had higher mean age, proportion of men, and rates of sublobar resection and squamous cell carcinoma than those without ILD. After matching, there was no significant difference in postoperative mortality rates between the control and ILD groups. The 5-year survival rate was significantly lower in the ILD group (66%) than in the control group (78.8%; P= .007). The 5-year survival rate of the ILD-GAP (Gender, Age, Physiology) stage III group (12.6%) was significantly lower than that of the ILD-GAP stage I (73.5%) and II groups (72.6%; P< .0001). Multivariable Cox analysis demonstrated that idiopathic pulmonary fibrosis, higher clinical stage, and recurrence were independent prognostic factors for mortality. ConclusionConcomitant ILD negatively affects long-term prognosis after lung cancer surgery, and ILD subtype and physiological severity assessment help predict prognosis after surgery.

The significance of elevated tumor markers among patients with interstitial lung diseases

The clinical implication of using serum tumor markers in patients with interstitial lung disease (ILD) is inconclusive. In this retrospective study, we analyzed the data of 1176 subjects (294 with ILDs and 882 healthy controls). Eligible patients were who had at least one or more available tumor marker results [carbohydrate antigen (CA) 19-9, CA 125, and carcinoembryonic antigen (CEA)] with no evidence of malignancies or other benign diseases that could be related to the increasing concentration of the values. The healthy controls selected from a health screening program were also screened for the presence of active cancer, and matched at a ratio of 1:3 with age and sex. The proportion of patients with abnormal values in the ILD group (121, idiopathic pulmonary fibrosis (IPF); 173, non-IPF-ILDs) was higher than in the matched control group (CEA, 21.5% vs. 5.5%; CA 19-9, 27.9% vs. 4.0%; CA 125, 36.4% vs. 2.0%). In the multivariable analysis, higher CEA levels were associated with shorter survival after adjusting for age, sex, lung function, and ILD subtypes (hazard ratio: 2.323, 95% confidence interval: 1.271–4.248, P = 0.006). In subgroup analysis, CEA remained a prognostic factor in patients with non-IPF-ILDs, but not in those with IPF.

NINTEDANIB CESSATION IN WAITLISTED LUNG TRANSPLANT CANDIDATES IS NOT ASSOCIATED WITH INCREASED WAITLIST MORTALITY OR PERIOPERATIVE COMPLICATIONS

NINTEDANIB CESSATION IN WAITLISTED LUNG TRANSPLANT CANDIDATES IS NOT ASSOCIATED WITH INCREASED WAITLIST MORTALITY OR PERIOPERATIVE COMPLICATIONS

Associations between shortened telomeres and rheumatoid arthritis-associated interstitial lung disease among U.S. Veterans

BackgroundShortened telomeres are associated with several different subtypes of interstitial lung disease (ILD), although studies of telomere length and ILD in rheumatoid arthritis (RA) are lacking. MethodsWithin the Veterans Affairs Rheumatoid Arthritis (VARA) registry, we performed cross-sectional and case-control studies of prevalent and incident ILD, respectively. We randomly selected a subset of RA patients with ILD and individually matched them to RA patients without ILD according to age, sex, and VARA enrollment date. Telomere length was measured on peripheral blood leukocytes collected at registry enrollment using quantitative PCR (T/S ratio). Short telomeres were defined as a T/S ratio in the lowest 10th percentile of the cohort. ResultsOur cross-sectional study cohort was comprised of 54 RA-ILD patients and 92 RA-non-ILD patients. T/S ratios significantly differed between patients with and without prevalent ILD (1.56 [IQR 1.30, 1.78] vs. 1.96 [IQR 1.65, 2.27], p < 0.001). Similarly, prevalence of ILD was significantly higher in patients with short vs. normal-length telomeres (73.3% vs. 32.8%, p = 0.002). Short telomeres were independently associated with an increased odds of prevalent ILD compared to normal-length telomeres (adjusted OR 6.60, 95% CI 1.78–24.51, p = 0.005). In our case-control analysis, comprised of 22 incident RA-ILD cases and 36 RA-non-ILD controls, short telomeres were not associated with incident RA-ILD (adjusted OR 0.90, 95% CI 0.06–13.4, p = 0.94). ConclusionShort telomeres were strongly associated with prevalent but not incident ILD among patients with RA. Additional studies are needed to better understand telomere length dynamics among RA patients with and without ILD.

Environmental and occupational exposures in interstitial lung disease.

We highlight recent advances in the understanding of how environmental and occupational exposures increase the risk of developing interstitial lung disease (ILD), and how to evaluate a patient for potential exposures. A review of emerging literature suggests that environmental and occupational exposures can be directly causal, as in the case of the pneumoconioses and smoking-related ILDs, or one of many contributors to disease, as in the case of idiopathic pulmonary fibrosis (IPF). Regardless of the level of association, exposures are clearly prevalent across all ILD subtypes studied. Inhalational exposures are increasingly recognized as an important component in the development of ILDs, and novel exposure-disease associations continue to be discovered. These exposures represent potential opportunities for further understanding the pathobiology of disease and for the prevention of these often progressive and debilitating disorders. Prospective, comprehensive data collection regarding occupational and environmental exposures are needed in ILD patients to fully elucidate specific antigens and their relationships to disease incidence and outcomes. Systematically collected exposure information will also inform potential interventions to remediate exposures and thus mitigate the course of frequently progressive and fatal diseases.

Perceptions of Genetic Testing: A Mixed-Methods Study of Patients with Pulmonary Fibrosis and Their First-Degree Relatives.

Rationale: Genetic testing is an emerging tool in interstitial lung disease (ILD) as several ILD subtypes have potential genetic causes or predispositions with resultant clinical implications. There is a need to understand the perceptions of patients and their first-degree relatives of genetic testing for ILD. Objectives: The objective of this study was to investigate patients with ILD and their first-degree family members' understanding of the genetic risks associated with ILD and their interest and/or concerns about genetic testing. Methods: This mixed-methods study included patients with ILD and their first-degree relatives. Data were obtained from an online survey and three focus groups. Categorical data were reported with descriptive frequencies. Chi-square analyses were used to measure associations. Focus group discussions were transcribed, coded, and analyzed according to the grounded theory principle. Results: A total of 188 respondents completed the survey; 119 patients, 52 first-degree relatives, and 17 who were both patients and who also reported being a first-degree relative to someone with ILD. Most (79%) patients had idiopathic pulmonary fibrosis. The majority of patients and first-degree relatives were unsure if there was a genetic cause, whereas 71% of those who were both patient and first-degree relative thought there could be a genetic cause to their ILD. Fifty-nine percent of respondents worried their family members could be affected, and 72% of respondents were interested in genetic testing. Interest in genetic testing was associated with sex (P = 0.03), post-secondary education (P = 0.047), and having a family member with ILD (P = 0.02). The primary motivators were understanding risk to family members and contributing to research. First-degree relatives were concerned about insurance issues (60%) and personal stress (60%) more often than patients (40% and 28%, respectively); 29% of first-degree relatives anticipated changing their health behavior based on results. Focus group themes included disease knowledge, understanding the role of genetics in ILD, testing concerns, and how to use genetic testing information. Conclusions: This study provides insight into the perceptions of patients and first-degree relatives of ILD-related genetic testing. These findings inform the need for additional patient resources, yet a better understanding of the clinical applications of ILD genetic testing and how testing may impact diagnostics, therapeutics, and prognostication.

Inhalational exposures in patients with fibrotic interstitial lung disease: Presentation, pulmonary function and survival in the Canadian Registry for Pulmonary Fibrosis.

Background and objectiveInhalational exposures are a known cause of interstitial lung disease (ILD), but little is understood about their prevalence across ILD subtypes and their relationship with pulmonary function and survival.MethodsPatients with fibrotic ILD were identified from the multicentre Canadian Registry for Pulmonary Fibrosis. Patients completed questionnaires regarding ILD‐related occupational and environmental exposures. The relationship between exposures and the outcomes of baseline age, gender, family history, pulmonary function and survival was analysed using linear and logistic regression models, linear mixed‐effect regression models and survival analysis using multivariable Cox proportional hazards along with the log‐rank test.ResultsThere were 3820 patients included in this study, with 2385 (62%) having ILD‐related inhalational exposure. Exposed patients were younger, particularly in the idiopathic pulmonary fibrosis subgroup. Inhalational exposure was associated with male gender (adjusted OR 1.46, 95% CI 1.28–1.68, p < 0.001) and family history of pulmonary fibrosis (adjusted OR 1.73, 95% CI 1.40–2.15, p < 0.001). Patients with any inhalational exposure had improved transplant‐free survival (hazard ratio 0.81, 95% CI 0.71–0.92, p = 0.001); this effect persisted across diagnostic subtypes. The relationship between exposures and annual change in forced vital capacity varied by ILD subtype.ConclusionPatients with fibrotic ILD report high prevalence of inhalational exposures across ILD subtypes. These exposures were associated with younger age at diagnosis, male gender and family history of pulmonary fibrosis. Identification of an inhalational exposure was associated with a survival benefit. These findings suggest that inhaled exposures may impact clinical outcomes in patients with ILD, and future work should characterize the mechanisms underlying these relationships.

Predicting Usual Interstitial Pneumonia Histopathology From Chest CT Imaging With Deep Learning

Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal form of interstitial lung disease (ILD) characterized by the absence of a known cause and usual interstitial pneumonitis (UIP) pattern on chest CT imaging and/or histopathology. Distinguishing UIP/IPF from other ILD subtypes is essential given different treatments and prognosis. Lung biopsy is necessary when noninvasive data are insufficient to render a confident diagnosis. Can we improve noninvasive diagnosis of UIP be improved by predicting ILD histopathology from CT scans by using deep learning? This study retrospectively identified a cohort of 1,239 patients in a multicenter database with pathologically proven ILD who had chest CT imaging. Each case was assigned a label based on histopathologic diagnosis (UIP or non-UIP). A custom deep learning model was trained to predict class labels from CT images (training set, n=894) and was evaluated on a 198-patient test set. Separately, two subspecialty-trained radiologists manually labeled each CT scan in the test set according to the 2018 American Thoracic Society IPF guidelines. The performance of the model in predicting histopathologic class was compared against radiologists' performance by using area under the receiver-operating characteristic curve as the primary metric. Deep learning model reproducibility was compared against intra-rater and inter-rater radiologist reproducibility. For the entire cohort, mean patient age was 62 ± 12 years, and 605 patients were female (49%). Deep learning performance was superior to visual analysis in predicting histopathologic diagnosis (area under the receiver-operating characteristic curve, 0.87 vs0.80, respectively; P< .05). Deep learning model reproducibility was significantly greater than radiologist inter-rater and intra-rater reproducibility (95%CI for difference in Krippendorff's alpha did not include zero). Deep learning may be superior to visual assessment in predicting UIP/IPF histopathology from CT imaging and may serve as an alternative to invasive lung biopsy.

Treatment outcomes of the interstitial lung disease subtype of unclassifiable type Mycobacterium avium complex pulmonary disease

BackgroundWe aimed to investigate treatment outcomes according to the presence or absence of cavitary lesions in patients with the interstitial lung disease (ILD) subtype of unclassifiable type Mycobacterium avium complex (MAC) pulmonary disease (PD). MethodsStudy subjects were enrolled at a tertiary referral center in South Korea from 2001 to 2020. Among patients with MAC-PD who had ILD as an underlying disease, 38 patients who were diagnosed with the ILD subtype of unclassifiable MAC-PD and who received treatment for ≥1 year were selected for this study. Treatment outcomes in terms of microbiological cure at 1 year were retrospectively analyzed for these patients. ResultsThe mean age of the patients was 64.4 ± 12.9 years, and 63.2% were male. The presence of cavitary lesions was noted in 68.4% (26/38) patients. A usual interstitial pneumonia pattern was the predominant type of ILD, which was identified in 26 (68.4%) patients. The overall 1-year microbiological cure rate of the 38 patients was 65.8% (25/38). Of the 26 patients with cavitary lesions, microbiological cure at 1 year was achieved in 14 patients (53.8%), which is significantly lower than that in patients without cavitary lesions (91.7%, 11/12, p = 0.030). ConclusionsA clear difference in treatment outcomes was noted in the ILD subtype of MAC-PD according to the presence or absence of cavitary lesions.

Interstitial Lung Disease in Firefighters: An Emerging Occupational Hazard.

IntroductionOccupational risk factors for interstitial lung disease (ILD) are a remediable aspect of this progressive pulmonary disorder. The association between firefighting and ILD is unknown. Our objective was to assess the characteristics of firefighters with ILD from a large single-center ILD registry.MethodsThe University of Chicago ILD database was reviewed for patients with a history of firefighting. Clinical information was abstracted from the medical record. The prevalence rate ratio of firefighters in the database compared to the baseline prevalence of firefighting in the Chicago metropolitan area was calculated via the Poisson distribution.ResultsNineteen firefighters were identified; all were men. A variety of ILD subtypes were seen across the cohort, including four patients with a diagnosis of connective tissue disease. Patients had mild forced vital capacity (FVC) and moderate diffusing capacity for carbon monoxide (DLCO) decrements on presentation; three patients died and two received lung transplantation over an average follow-up time of 76 months. Firefighters were seen at a greater proportion in the ILD registry than in the general population with a prevalence rate ratio of 3.98.ConclusionsFirefighting was overrepresented in our cohort compared to the general population, suggesting that there may be a causative association between firefighting and the presence of ILD. The wide variety of ILD subtypes observed suggest that all ILD patients should be asked about their occupational history. Further investigation to identify occupational exposures and determine the benefit of remediation is needed.

Perioperative Management of Patients with Idiopathic Pulmonary Fibrosis Undergoing Noncardiac Surgery: A Narrative Review.

PurposeThe idiopathic interstitial pneumonias (IIP) constitute a large cohort of the over 200 subtypes of interstitial lung disease (ILD). Idiopathic pulmonary fibrosis (IPF) is the most widely studied, arguably the most severe etiology of ILD and the most common IIP diagnosis. The objective of this narrative review is to outline the current evidence on optimal perioperative management of IPF. PubMed, Embase and Web of Science were analyzed for appropriate peer-reviewed references by utilizing key word search (“interstitial lung disease” OR “idiopathic pulmonary fibrosis” OR “idiopathic interstitial pneumonitis” OR “ILD” OR “IPF” AND “surgery” OR “anesthesia” OR “perioperative”) within the past thirty years (1990-current). Non-English language references were excluded. A total of 205 references were curated by the authors. Eighty-seven consensus statements, clinical trials, retrospective cohort studies or case series met criteria and were incorporated into the findings of this narrative review.ConclusionAfter review, we conclude that complications, dominated by postoperative pulmonary complications, pose a significant barrier to safe perioperative care of patients with IPF. Ensuring that the preoperative IPF patient has been medically optimized is important for minimizing this risk. Initial assessment of the ARISCAT score, pulmonary function studies and cardiopulmonary exercise testing may identify IPF patients at particularly high perioperative pulmonary risk. Identifying IPF patients with 6–12-month declines in DLCO of >15%, V02max <8.3 mL/kg/min, <80% predicted value FVC, a 50-meter reduction in the 6MWT or preoperative home oxygen use may be helpful in preoperative risk stratification. Medically optimizing treatable co-morbidities should be a priority in preoperative assessment. Regional or neuraxial anesthesia should be considered an optimal technique for the avoidance of general anesthesia related complications when indicated. Acute exacerbation and postoperative pneumonia have been identified as important postsurgical complications in both thoracic and nonthoracic surgical populations.

Prevalence and lethality of interstitial pulmonary diseases in the Region of Los Ríos, Chile

Idiopathic Pulmonary Fibrosis (IPF) is a subtype of interstitial lung disease (ILD) that significantly affects people's quality of life, whose prevalence and mortality has increased. To determine the prevalence and lethality of ILD in the Los Ríos Region between the years 2018 and 2019. Review of a database of all patients attended at an outpatient clinic of the regional hospital. Those patients with the diagnosis of ILD and seen between 2018 and 2019 were selected. Mortality and its causes were verified with death certificates. In the study period, 339 cases with ILD, aged 71 ± 10 years (64% women) were identified. The calculated ILD prevalence was 84 cases per 100,000 inhabitants, with a higher predominancy in Futrono and Paillaco communes. IPF and Connective Tissue Diseases were the predominant subtypes. Overall lethality was 18%, with more deaths among patients with IPF (n = 31). In the Los Ríos Region, ILDs have a relevant prevalence and lethality.

Proteomic biomarkers of progressive fibrosing interstitial lung disease: a multicentre cohort analysis

Progressive fibrosing interstitial lung disease (ILD) is characterised by parenchymal scar formation, leading to high morbidity and mortality. The ability to predict this phenotype remains elusive. We conducted a proteomic analysis to identify novel plasma biomarkers of progressive fibrosing ILD and developed a proteomic signature to predict this phenotype. Relative plasma concentrations for 368 biomarkers were determined with use of a semi-quantitative, targeted proteomic platform in patients with connective tissue disease-associated ILD, chronic hypersensitivity pneumonitis, or unclassifiable ILD who provided research blood draws at the University of California (discovery cohort) and the University of Texas (validation cohort). Univariable logistic regression was used to identify individual biomarkers associated with 1-year ILD progression, defined as death, lung transplant, or 10% or greater relative forced vital capacity (FVC) decline. A proteomic signature of progressive fibrosing ILD was then derived with use of machine learning in the University of California cohort and validated in the University of Texas cohort. The discovery cohort comprised 385 patients (mean age 63·6 years, 59% female) and the validation cohort comprised 204 patients (mean age 60·7 years, 61% female). 31 biomarkers were associated with progressive fibrosing ILD in the discovery cohort, with 17 maintaining an association in the validation cohort. Validated biomarkers showed a consistent association with progressive fibrosing ILD irrespective of ILD clinical diagnosis. A proteomic signature comprising 12 biomarkers was derived by machine learning and validated in the University of Texas cohort, in which it had a sensitivity of 0·90 and corresponding negative predictive value of 0·91, suggesting that approximately 10% of patients with a low-risk proteomic signature would experience ILD progression in the year after blood draw. Those with a low-risk proteomic signature experienced an FVC change of +85·7 mL (95% CI 6·9 to 164·4) and those with a high-risk signature experienced an FVC change of -227·1 mL (-286·7 to -167·5). A theoretical clinical trial restricted to patients with a high-risk proteomic signature would require 80% fewer patients than one designed without regard to proteomic signature. 17 plasma biomarkers of progressive fibrosing ILD were identified and showed consistent associations across ILD subtypes. A proteomic signature of progressive fibrosing ILD could enrich clinical trial cohorts and avoid the need for antecedent progression when defining progressive fibrosing ILD for clinical trial enrolment. National Heart Lung and Blood Institute.

Interstitial lung diseases associated with mutations of poly(A)-specific ribonuclease: A multicentre retrospective study.

Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations. We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network. We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n=12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n=13), antifibrotic agents (n=11), immunosuppressants (n=5) and N-acetyl cysteine (n=2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation. IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.

Efficacy of inspiratory muscle training on inspiratory muscles strength, functional capacity, and quality of life in patients with interstitial lung disease. A single non-controlled clinical study

IntroductionThe aim of this study was to investigate the effectiveness of low level laser therapy (extravascular laser blood irradiation) on glycaemic levels in type 2 diabetes mellitus patients The most disabling symptoms in interstitial lung disease (ILD) patients are exertional dyspnoea, functional limitations, and impaired quality of life (QoL), all related to inspiratory muscle dysfunction. Therefore, the purpose of this study was to investigate the impact of inspiratory muscle training by using a threshold device on inspiratory muscle strength, functional capacity, and QoL in patients with ILD.MethodsA single non-controlled clinical study was conducted among 30 patients with different subtypes of ILD who received 30-minute threshold inspiratory muscle training 3 times per week for 12 weeks at 30% of the maximum inspiratory pressure (PI&lt;sub&gt;max&lt;/sub&gt;). PI&lt;sub&gt;max&lt;/sub&gt;, distance walked in a 2-minute walk test (2MWT), oxygen saturation (SO&lt;sub&gt;2&lt;/sub&gt;%), and QoL by the 36-item Short-Form Health Survey were measured before and after the intervention.ResultsA significant improvement was observed in all measured variables: PI&lt;sub&gt;max&lt;/sub&gt; (&lt;i&gt;p&lt;/i&gt; = 0.0001), distance walked in 2MWT (&lt;i&gt;p&lt;/i&gt; = 0.003), SO&lt;sub&gt;2&lt;/sub&gt;% (&lt;i&gt;p&lt;/i&gt; = 0.043), and the QoL score (&lt;i&gt;p&lt;/i&gt; &lt; 0.05).ConclusionsIt was found that threshold inspiratory muscle training is recommended to be a part of the routine care for ILD patients to gain the benefits of improving the control of the symptoms.

Comparing outcomes of ILD patients managed in specialised versus non-specialised centres

BackgroundEarly appropriate diagnosis and treatment of interstitial lung diseases (ILD) is crucial to slow disease progression and improve survival. Yet it is unknown whether initial management in an expert centre is associated with improved outcomes. Therefore, we assessed mortality, hospitalisations and health care costs of ILD patients initially diagnosed and managed in specialised ILD centres versus non-specialised centres and explored differences in pharmaceutical treatment patterns.MethodsAn epidemiological claims data analysis was performed, including patients with different ILD subtypes in Germany between 2013 and 2018. Classification of specialised centres was based on the number of ILD patients managed and procedures performed, as defined by the European Network on Rare Lung Diseases. Inverse probability of treatment weighting was used to adjust for covariates. Mortality and hospitalisations were examined via weighted Cox models, cost differences by weighted gamma regression models and differences in treatment patterns with weighted logistic regressions.ResultsWe compared 2022 patients managed in seven specialised ILD centres with 28,771 patients managed in 1156 non-specialised centres. Specialised ILD centre management was associated with lower mortality (HR: 0.87, 95% CI 0.78; 0.96), lower all-cause hospitalisation (HR: 0.93, 95% CI 0.87; 0.98) and higher respiratory-related costs (€669, 95% CI €219; €1156). Although risk of respiratory-related hospitalisations (HR: 1.00, 95% CI 0.92; 1.10) and overall costs (€− 872, 95% CI €− 75; €1817) did not differ significantly, differences in treatment patterns were observed.ConclusionInitial management in specialised ILD centres is associated with improved mortality and lower all-cause hospitalisations, potentially due to more differentiated diagnostic approaches linked with more appropriate ILD subtype-adjusted therapy.