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Background and Objective: Interstitial lung diseases (ILDs) encompass over 200 entities. Among them, fibrosing lung diseases, have recently generated special interest due to the emerging therapies for their management. However, it is important to deepen our knowledge of other less prevalent ILD, since many of them are associated with a poor prognosis. This narrative review aims to provide a practical and up-to-date description of some poorly recognized ILD. It covers rare idiopathic interstitial pneumonias and their histologic patterns, genetic disorders with interstitial lung involvement (Hermansky-Pudlak syndrome), and ILD associated with benign proliferation of pulmonary lymphoid tissue, namely follicular bronchiolitis and granulomatous-lymphocytic interstitial lung disease., Methods: Electronic searches of PubMed and Google Scholar using specific keywords were conducted. Articles underwent screening for relevance, covering review articles, meta-analyses, systematic reviews, case series, prospective studies, society guidelines, editorials in peer-reviewed journals; scientific books on the subject. The data included was limited to English and Spanish publications., Key Content and Findings: Despite the low prevalence of these diseases, the increased recognition of radiological patterns, pathological features, and diagnostic procedures, have permitted their better characterization. This review highlights epidemiology, clinical presentation, diagnosis, natural history, and treatment., Conclusions: Lesser-studied ILD represent a diagnostic and therapeutic challenge and can be frequently misdiagnosed. Also, due to the lack of randomized controlled trials, there are no well-established therapeutic options. Further studies or registries are needed to improve accurate diagnosis and management., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-450/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Fibrotic hypersensitivity pneumonitis (HP) has a poor prognosis when no antigen is identified, which occurs in many cases. We present a case of HP due to foam exposure in bedding, an unrecognised cause of HP. A woman was referred for dyspnoea and cough. High-resolution chest computed tomography (HRCT) showed a three-density pattern with gas trapping. Pulmonary function tests (PFTs) revealed restriction and reduced diffusing capacity. Bronchoalveolar lavage showed lymphocytosis (43%) and lung cryobiopsy showed fibrosis, lymphocytic infiltration and multinucleated giant cells. She had foam in mattress and pillows but no other exposures. Her symptoms, PFTs, and imaging improved after avoiding foam in her bedding. After re-exposure to a foam pillow, her symptoms, PFTs, and HRCT worsened. Microbiological analysis of the foam pillow reported Penicillium spp , known to cause HP. Foam exposure is a novel cause of HP, and foam avoidance can prevent disease progression and death., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A machine learning classifier system, Fibresolve, was designed and validated as an adjunct to non-invasive diagnosis in idiopathic pulmonary fibrosis (IPF). The system uses a deep learning algorithm to analyze chest computed tomography (CT) imaging. We hypothesized that Fibresolve is a useful predictor of mortality in interstitial lung diseases (ILD)., Methods: Fibresolve was previously validated in a multi-site >500-patient dataset. In this analysis, we assessed the usefulness of Fibresolve to predict mortality in a subset of 228 patients with IPF and other ILDs in whom follow up data was available. We applied Cox regression analysis adjusting for the Gender, Age, and Physiology (GAP) score and for other known predictors of mortality in IPF. We also analyzed the role of Fibresolve as tertiles adjusting for GAP stages., Results: During a median follow-up of 2.8 years (range 5 to 3434 days), 89 patients died. After adjusting for GAP score and other mortality risk factors, the Fibresolve score significantly predicted the risk of death (HR: 7.14; 95% CI: 1.31-38.85; p = 0.02) during the follow-up period, as did forced vital capacity and history of lung cancer. After adjusting for GAP stages and other variables, Fibresolve score split into tertiles significantly predicted the risk of death (p = 0.027 for the model; HR 1.37 for 2nd tertile; 95% CI: 0.77-2.42. HR 2.19 for 3rd tertile; 95% CI: 1.22-3.93)., Conclusions: The machine learning classifier Fibresolve demonstrated to be an independent predictor of mortality in ILDs, with prognostic performance equivalent to GAP based solely on CT images., Competing Interests: Declaration of competing interest JR, AK, and MM are employees and owners at IMVARIA Inc. OMM and AS have no conflict of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Early and integrated palliative care is recommended for patients with idiopathic pulmonary fibrosis. Unfortunately, palliative care delivery remains poor due to various barriers in practice. This study describes various palliative care delivery models in a real-world cohort of patients with idiopathic pulmonary fibrosis, examines the predictors of survival in this cohort of patients, and explores the impact of palliative care on survival. Design: Charts were reviewed retrospectively and analyzed. The primary outcome was survival during a 4-year follow-up period. Two multivariable models were created to examine the impact of therapeutic strategies including palliative intervention on survival. Results: 298 patients with idiopathic pulmonary fibrosis were enrolled from 3 interstitial lung disease clinics with different palliative care models in Edmonton, Canada; Bristol, UK; and Kingston, Canada. 200 (67%) patients received palliative care and 119 (40%) died during follow up. Primary palliative care models (Edmonton and Bristol) delivered palliative care to 96% and 100% respectively compared 21% in the referral model (Queens). Palliative care [adjusted hazard ratio (aHR) .28 (.12-.65)] along with the use of antifibrotics [aHR .56 (.37-.84)], and body mass index >30 [aHR .47 (.37-.85)] reduced the risk of death in our idiopathic pulmonary fibrosis cohort. Opioid use was associated with worse survival [aHR 2.11 (1.30-23.43)]. Conclusions: Both palliative care and antifibrotic use were associated with survival benefit in this cohort of patients with idiopathic pulmonary fibrosis after adjusting for covariates. The benefit was seen despite differences in disease severity and different palliative care delivery models., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Dr Asai declares honoraria and speaker fees from Sanofi, Pfizer, AbbVie, Leo, Sun Pharma, Novartis, Miravo, Eli Lilly, Kyowa Kirin, and L’Oreal; research and education grants from Sanofi Canada, AbbVie, Pfizer, Novartis, the Canadian Dermatology Foundation, and the Eczema Society of Canada; and performs clinical trials for Novartis and Leo. Author Wilken and Drs Moran-Mendoza and Pourafkari have no conflicts of interest to declare.

Background: The precise mechanisms driving poor exercise tolerance in patients with fibrotic interstitial lung diseases (fibrotic ILDs) showing a severe impairment in single-breath lung diffusing capacity for carbon monoxide (D LCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O 2 transfer, a severely impaired D LCO may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD., Methods: Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing D LCO < 40%) and 22 controls underwent pulmonary function tests and an incremental cardiopulmonary exercise test with serial measurements of operating lung volumes and 0-10 Borg dyspnea and leg discomfort scores., Results: Subjects from the D LCO < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired D LCO ( P < .05). Peak work rate was ∼45% (vs controls) and ∼20% (vs D LCO > 40%) lower in the former group, being associated with lower (and flatter) O 2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower S pO 2 . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the D LCO < 40% group ( P < .05). In association with the greatest leg discomfort scores, they reported the highest dyspnea scores at a given work rate. Between-group differences lessened or disappeared when dyspnea intensity was related to indexes of increased demand-capacity imbalance, that is, decreasing submaximal, dynamic ventilatory reserve, and inspiratory reserve volume/total lung capacity ( P > .05)., Conclusions: A severely reduced D LCO in fibrotic ILD signals multiple interconnected derangements (cardiovascular impairment, an early shift to anaerobic metabolism, excess ventilation, inspiratory constraints, and hypoxemia) that ultimately lead to limiting respiratory (dyspnea) and peripheral (leg discomfort) symptoms. D LCO < 40%, therefore, might help in clinical decision-making to indicate the patient with fibrotic ILD who might derive particular benefit from pharmacologic and non-pharmacologic interventions aimed at lessening these systemic abnormalities., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Purpose: Cerebral hypoxia may exacerbate the perception of fatigue. We previously demonstrated that exercise-related hypoxemia, a hallmark of fibrotic interstitial lung disease ( f -ILD), dose dependently impairs cerebral oxygenation in these patients. It is unknown whether normalizing cerebral oxygenation with O 2 supplementation would be associated with positive changes in a relevant patient-centered outcome during exercise in f -ILD, such as improved perceived fatigue., Methods: Fourteen patients (12 males, 72 ± 8 yr, 8 with idiopathic pulmonary fibrosis, lung diffusing capacity for carbon monoxide = 44% ± 13% predicted) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) breathing medical air. Fourteen controls cycled up to Tlim of an age- and sex-matched patient. Patients repeated the test on supplemental O 2 (fraction of inspired O 2 = 0.41 ± 0.08) for the same duration. Near-infrared spectroscopy and the rating-of-fatigue (ROF) scale assessed prefrontal cortex oxygenation and perceived fatigue, respectively., Results: Patients showed severe exertional hypoxemia (Tlim O 2 saturation by pulse oximetry = 80% ± 8%); they had poorer cerebral oxygenation (e.g., oxy-deoxyhemoglobin difference [HbDiff] = -3.5 ± 4.7 [range = -17.6 to +1.9] vs +1.9 ± 1.7 μmol from rest) and greater fatigue (ROF = 6.2 ± 2.0 vs 2.6 ± 2.3) versus controls under air ( P < 0.001). Reversal of exertional hypoxemia with supplemental O 2 led to improved HbDiff (+1.7 ± 2.4 μmol from rest; no longer differing from controls) and lower ROF scores (3.7 ± 1.2, P < 0.001 vs air) in patients. There was a significant correlation between O 2 -induced changes in HbDiff and ROF scores throughout exercise in f -ILD ( rrepeated-measures correlation = -0.51, P < 0.001)., Conclusions: Supplemental O 2 improved cerebral oxygenation during exercise in f -ILD, which was moderately associated with lower ratings of perceived fatigue. Reversing cerebral hypoxia with O 2 supplementation may thus have positive effects on patients' disablement beyond those expected from lower ventilation and dyspnea in this patient population., (Copyright © 2023 by the American College of Sports Medicine.)

Background: Most interstitial lung diseases (ILDs) manifest with a restrictive ventilatory defect as the common physiologic abnormality. Low carbon monoxide diffusing capacity (Dlco) is considered to be the earliest abnormality on pulmonary function tests (PFTs) in patients with ILD. However, its measurement requires complex and expensive equipment. Our study aimed to assess if high expiratory flows are the earliest PFT abnormality in patients with idiopathic pulmonary fibrosis (IPF) and ILD., Methods: In a real-world cohort of incident cases with ILD, we identified the initial PFTs on all patients newly diagnosed with ILD at Kingston Health Sciences Center (in Kingston, Ontario, Canada) between 2013 and 2017. The diagnosis of ILD, including IPF, was established as per current guidelines. Among patients with normal forced vital capacity (FVC), total lung capacity (TLC), and Dlco, we assessed the frequency of high expiratory flows defined as forced expiratory volume in 1 s (FEV 1 )/FVC, FEF 25 , FEF 25-75 , FEF 75, and peak expiratory flow > 95% confidence limit of normal. We adjusted for emphysema, increased airway resistance, and obesity., Results: We assessed PFTs of 289 patients with ILD; 88 (30%) of them had normal FVC, TLC, and Dlco. Among these, high FEV1/FVC was the most common abnormality in 37% of patients, in 43% of nonobese patients, and in 58% of those with no emphysema and normal airway resistance. Results were similar in the 88 patients with IPF., Conclusions: High FEV1/FVC could allow identifying patients with ILD/IPF in the earliest stages of their disease with simple spirometry, leading to earlier diagnosis and treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Thoracic Medicine.)

The functional disturbances driving "out-of-proportion" dyspnoea in patients with fibrosing interstitial lung disease (f-ILD) showing only mild restrictive abnormalities remain poorly understood. Eighteen patients (10 with idiopathic pulmonary fibrosis) showing preserved spirometry and mildly reduced total lung capacity (≥70% predicted) and 18 controls underwent an incremental cardiopulmonary exercise test with measurements of operating lung volumes and Borg dyspnoea scores. Patients' lower exercise tolerance was associated with higher ventilation (V̇ E )/carbon dioxide (V̇CO 2 ) compared with controls (V̇ E /V̇CO 2 nadir=35 ± 3 versus 29 ± 2; p < 0.001). Patients showed higher tidal volume/inspiratory capacity and lower inspiratory reserve volume at a given exercise intensity, reporting higher dyspnoea scores as a function of both work rate and V̇ E . Steeper dyspnoea-work rate slopes were associated with lower lung diffusing capacity, higher V̇ E /V̇CO 2 , and lower peak O 2 uptake (p < 0.05). Heightened ventilatory demands in the setting of progressively lower capacity for tidal volume expansion on exertion largely explain higher-than-expected dyspnoea in f-ILD patients with largely preserved dynamic and "static" lung volumes at rest., (Copyright © 2023. Published by Elsevier B.V.)

This study suggests that interventions geared to improve peripheral factors of performance fatigability during exercise in interstitial lung disease may prove valuable to decrease patients' perceived fatigability, since both seem closely related https://bit.ly/3lpIUPs., Competing Interests: Conflict of interest: M. Marillier was a recipient of a Long-Term Research Fellowship (LTRF 2018) from the European Respiratory Society to support his post-doctoral stay at Queen's University. J.A. Neder is an associate editor of this journal. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Hypoxaemia and cardiocirculatory abnormalities may impair muscle oxygen (O 2 ) delivery relative to O 2 requirements thereby increasing the rate of O 2 extraction during incremental exercise in fibrotic interstitial lung disease (f-ILD). Using changes in deoxyhaemoglobin concentration ([HHb]) by near-infrared spectroscopy (NIRS) as a proxy of O 2 extraction, we investigated whether a simplified (double-linear) approach, previously tested in heart failure, would provide useful estimates of muscle deoxygenation in f-ILD., Methods: A total of 25 patients (23 men, 72 ± 8 years; 20 with idiopathic pulmonary fibrosis, lung diffusing capacity for carbon monoxide = 44 ± 11% predicted) and 12 age- and sex-matched healthy controls performed incremental cycling to symptom limitation. Changes in vastus lateralis [HHb] assessed by NIRS were analysed in relation to work rate (WR) and O 2 uptake throughout the exercise., Results: Patients showed lower exercise capacity than controls (e.g., peak WR = 67 ± 18% vs. 105 ± 20% predicted, respectively; p < 0.001). The [HHb] response profile was typically S-shaped, presenting three distinct phases. Exacerbated muscle deoxygenation in patients versus controls was evidenced by: (i) a steeper mid-exercise [HHb]-WR slope (0.30 ± 0.22 vs. 0.11 ± 0.08 μmol/W; p = 0.008) (Phase 2), and (ii) a larger late-exercise increase in [HHb] (p = 0.002) (Phase 3). Steeper [HHb]-WR slope was associated with lower peak WR (r = -0.70) and greater leg discomfort (r = 0.77; p < 0.001) in f-ILD., Conclusion: This practical approach to interpreting [HHb] during incremental exercise might prove useful to determine the severity of muscle deoxygenation and the potential effects of interventions thereof in hypoxemic patients with f-ILD., (© 2022 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic disease affecting the lung parenchyma and small airways. It typically results from an immune-mediated reaction provoked by an overt or occult inhaled antigen in susceptible individuals. The chronic or fibrotic form of HP has a poor prognosis, especially when no inciting antigen is identified, which occurs in up to 60% of cases. We report two cases of HP associated with exposure to mold in foam pillows and a mattress, which has not previously been reported as a risk factor for HP. Given the high prevalence of foam in pillows and mattresses, mold in foam in bedding may explain many HP cases with a previously unrecognized cause. Early identification and avoidance of foam in bedding may prevent HP progression to end-stage pulmonary fibrosis and death., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Exercise-induced hypoxaemia is a hallmark of chronic fibrotic interstitial lung disease ( f -ILD). It remains unclear whether patients' severe hypoxaemia may exaggerate locomotor muscle fatigue and, if so, to what extent oxygen (O 2 ) supplementation can ameliorate these abnormalities., Methods: Fifteen patients (12 males, 9 with idiopathic pulmonary fibrosis) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) while breathing medical air. Fifteen age-matched and sex-matched controls cycled up to patients' Tlim. Patients repeated the exercise test on supplemental O 2 (42%±7%) for the same duration. Near-infrared spectroscopy assessed vastus lateralis oxyhaemoglobin concentration ((HbO 2 )). Pre-exercise to postexercise variation in twitch force (∆Tw) induced by femoral nerve magnetic stimulation quantified muscle fatigue., Results: Patients showed severe hypoxaemia (lowest O 2 saturation by pulse oximetry=80.0%±7.6%) which was associated with a blunted increase in muscle (HbO 2) during exercise vs controls (+1.3±0.3 µmol vs +4.4±0.4 µmol, respectively; p<0.001). Despite exercising at work rates ∼ one-third lower than controls (42±13 W vs 66±13 W), ∆Tw was greater in patients (∆Tw/external work performed by the leg muscles=-0.59±0.21 %/kJ vs -0.25±0.19 %/kJ; p<0.001). Reversal of exertional hypoxaemia with supplemental O 2 was associated with a significant increase in muscle (HbO 2) , leading to a reduced decrease in ∆Tw in patients (-0.33±0.19 %/kJ; p<0.001 vs air). Supplemental O 2 significantly improved leg discomfort (p=0.005)., Conclusion: O 2 supplementation during exercise improves leg muscle oxygenation and fatigue in f -ILD. Lessening peripheral muscle fatigue to enhance exercise tolerance is a neglected therapeutic target that deserves clinical attention in this patient population., Competing Interests: Competing interests: MM was funded by a European Respiratory Society’s Long Term Fellowship and the John Alexander Stuart Fellowship, Queen’s University. JAN has been funded by the New Clinician Scientist Program from the Southeastern Ontario Academic Medical Association (SEAMO), Canada. His laboratory was established owing to the Canadian Foundation for Innovation’s John R. Evans Leaders Fund, Canada., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Disease behaviour may guide diagnosis and treatment decisions in patients with interstitial lung disease (ILD). STARLINER aimed to characterise disease behaviour in patients with suspected ILD during the peri-diagnostic period using real-time home-based assessments., Methods: STARLINER (NCT03261037) was an international, multicentre study. Patients ≥ 50 years old with suspected ILD were followed throughout the peri-diagnostic period, consisting of a pre-diagnostic period (from enrolment to diagnosis) and a post-diagnostic period (from diagnosis to treatment initiation). Study length was variable (≤ 18 months). The primary endpoint was time-adjusted semi-annual forced vital capacity (FVC) change measured during the peri-diagnostic period using daily home spirometry in patients with idiopathic pulmonary fibrosis (IPF). Secondary outcomes included changes in FVC (home spirometry) in patients with non-IPF ILD, changes in FVC (site spirometry), changes in physical functional capacity measured by daily home accelerometry and site 6-min walk distance (6MWD), and changes in patient-reported outcomes (PROs) in IPF or non-IPF ILD., Results: Of the 178 patients enrolled in the study, 68 patients were diagnosed with IPF, 62 patients were diagnosed with non-IPF ILD, 9 patients received a non-ILD diagnosis and 39 patients did not receive a diagnosis. Technical and analytical issues led to problems in applying the prespecified linear regression model to analyse the home FVC data. Time-adjusted median (quartile [Q]1, Q3) semi-annual FVC change during the peri-diagnostic period measured using home and site spirometry, respectively, was - 147.7 (- 723.8, 376.2) ml and - 149.0 (- 314.6, 163.9) ml for IPF and 19.1 (- 194.9, 519.0) ml and - 23.4 (- 117.9, 133.5) ml in non-IPF ILD. A greater decline in steps per day was observed for IPF versus non-IPF ILD, whereas an increase in 6MWD was observed for patients with IPF versus a decline in 6MWD for patients with non-IPF ILD. No clear patterns of disease behaviour were observed for IPF versus non-IPF ILD for PROs., Conclusions: Despite home spirometry being feasible for most patients and centres, technical and analytical challenges in the home-based assessments prevented firm conclusions regarding disease behaviour. This highlights that further optimisation of the technology and analysis methods is required before widespread implementation., Trial Registration: NCT03261037., (© 2021. The Author(s).)

Introduction: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) with a poor prognosis. Early diagnosis and treatment of IPF may increase lifespan and preserve quality of life. Chest CT is the best test to diagnose IPF, but it is expensive and impractical as a screening test. Fine crackles on chest auscultation may be the only best to screen for IPF., Methods: We prospectively assessed the presence and type of crackles on chest auscultation in all patients referred to the ILD Clinic at the Kingston Health Sciences Center in Ontario, Canada. Clinicians with varying levels of experience recorded the presence of fine crackles, coarse crackles or both independently and unaware of the final diagnosis. We applied multinomial logistic regression to adjust for ILD severity and factors that could affect the identification of crackles., Results: We evaluated 290 patients referred to the ILD Clinic. On initial presentation, 93% of patients with IPF and 73% of patients with non-IPF ILD had fine crackles on auscultation. In patients with IPF, fine crackles were more common than cough (86%), dyspnoea (80%), low diffusing capacity (87%), total lung capacity (57%) and forced vital capacity (50%). There was 90% observer agreement in identifying fine crackles at a subsequent visit. In multiple regression analysis, the identification of fine crackles was unaffected by lung function, symptoms, emphysema, chronic obstructive pulmonary disease, obesity or clinician experience (p>0.05)., Conclusions: Fine crackles on chest auscultation are a sensitive and robust screening tool that can lead to early diagnosis and treatment of patients with IPF., Competing Interests: Competing interests: OM-M has received consulting and speaking honoraria from Boehringer Ingelheim and F. Hoffmann-La Roche, none influencing this work. TR and SA declare no conflict of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

It is unknown whether hypoxemia, a hallmark of fibrotic interstitial lung disease (f-ILD), may impair cerebral oxygenation during exercise in these patients. Twenty-seven patients [23 males, 72 ± 8 years, lung diffusing capacity for carbon monoxide (DL CO ) = 44 ± 11 % predicted] and 12 controls performed an incremental bicycle test. Prefrontal oxygenation [tissue saturation index (TSI)] was assessed by near-infrared spectroscopy. Patients showed lower arterial O 2 saturation (SpO 2 ) and larger fall in cerebral TSI during exercise vs controls (p < 0.05). However, changes (Δ) from rest to peak-exercise in SpO 2 (-2.2 % to -26.9 %) and TSI (1.4 % to -16.6 %) varied substantially among patients. In the 16 patients showing significant cerebral deoxygenation (Δ TSI ≥ 4% based on controls), SpO 2 decreased more (-12.6 ± 6.7 % vs -5.7 ± 2.8 %, p = 0.001) and peak O 2 uptake was lower (68.3 ± 19.2 % vs 87.8 ± 24.8 % predicted, p = 0.03) vs their 11 counterparts. In association with DL CO and forced vital capacity, Δ cerebral TSI independently predicted peak O 2 uptake on multivariable regression analysis (R 2  = 0.54). Exertional hypoxemia impairs cerebral oxygenation in a dose-dependent fashion in f-ILD. Future studies are warranted to investigate whether this potentially reversible abnormality play a contributory role in limiting exercise tolerance in these patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Exertional dyspnea in interstitial lung disease (ILD) remains difficult to manage despite advances in disease-targeted therapies. Pulmonary opioid receptors present a potential therapeutic target for nebulized fentanyl to provide dyspnea relief., Methods: ILD patients were characterized with reference to healthy volunteers. A randomized, double-blind, placebo-controlled crossover comparison of 100 mcg nebulized fentanyl vs placebo on dyspnea intensity and inspiratory neural drive (IND) during constant work rate (CWR) cycle exercise was performed in 21 ILD patients., Results: Dyspnea intensity in ILD increased in association with an increase in IND (diaphragm activation) from a high resting value of 16.66 ± 6.52 %-60.04 ± 12.52 % of maximum (r = 0.798, p < 0.001). At isotime during CWR exercise, Borg dyspnea intensity ratings with fentanyl vs placebo were 4.1 ± 1.2 vs 3.8 ± 1.2, respectively (p = 0.174), and IND responses were also similar., Conclusion: IND rose sharply during constant work rate exercise in association with dyspnea intensity in mild to moderate ILD but was not different after nebulized fentanyl compared with placebo., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction : Idiopathic pulmonary fibrosis (IPF) is a debilitating, progressive, and fatal fibrotic pulmonary disease with a prognosis comparable to that of lung cancer. IPF management is a complex process that involves pharmacological and nonpharmacological interventions, extensive patient education, and addressing patient needs that change through the course of the illness. Areas covered : This review summarizes the key aspects of a multifaceted, multidisciplinary, individualized approach to IPF care that incorporates available treatment options, strategies to improve compliance with antifibrotic therapies, pulmonary rehabilitation, and the integration of palliative care for symptom management. Aspects of care discussed include the use of antifibrotic therapy and nonpharmacological treatments, targeted education and psychosocial support, evaluation and management of comorbidities, and early integration of palliative care. Expert opinion : By incorporating this comprehensive approach to disease management, physicians can address most aspects of care for a patient with IPF to optimize survival and quality of life.

Introduction: Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, with a median survival time of two to five years. Most patients with IPF experience chronic breathlessness, which is closely linked to poor perceived quality of life and significant restriction of daily activities; therefore, effective management of this distressing symptom is a major goal of patient care. Areas covered: This report summarizes the physiology of IPF during rest and exercise, outlines current concepts of the mechanisms of breathlessness, and provides a physiological rationale for optimal management of individual patients. It also examines the evidence for efficacy of a number of therapeutic interventions currently at our disposal for the management of breathlessness in IPF, which aim to reduce respiratory neural drive, reduce worsening of mechanical load, and alter central perception. Expert commentary: The current evidence supporting general measures in relieving chronic breathlessness is weak; hence, more carefully designed prospective studies are required.

Pulmonary eosinophilia (PE) can be found in very diverse pathological processes. Several medications have also been associated with this entity. Acetaminophen is a medication commonly used in multiple different drug formulations, many of which are available without a prescription. It has however been associated with pulmonary eosinophilia (eosinophilic pneumonia) in a few cases in Japan. We describe the case of a 68-year-old Caucasian female who presented with new persistent dry cough and dyspnea on exertion after she started using up to 4 grams of acetaminophen on a daily basis. Chest imaging revealed peripheral lower lung zone ground glass and reticular opacities, and increased eosinophils were present on bronchoalveolar lavage (BAL). The patient's symptoms markedly improved upon acetaminophen cessation, and significantly decreased eosinophils were seen on repeat BAL. To our knowledge, this is the first case of likely acetaminophen-induced pulmonary eosinophilia reported outside Japan.

Background: The lung function of patients with idiopathic pulmonary fibrosis (IPF) has not been characterized in detail. objective: To characterize the heterogeneous physiological abnormalities that exist in patients with IPF during their initial clinical evaluation., Methods: Lung function tests from 93 patients, performed within six months of the initial diagnosis of IPF, were obtained from a referral pulmonary function laboratory at a tertiary care hospital in Canada. A restrictive pattern was defined as total lung capacity (TLC) <95th percentile of predicted value. Patients with obstructive lung disease, lung cancer, emphysema and other restrictive lung diseases were excluded., Results: On diagnosis, 73% of patients with IPF had a restrictive pattern, with a mean TLC of 72% of predicted. Mean forced vital capacity (FVC) was 71% and 44% of patients had an FVC <95th percentile. Mean diffusing capacity for carbon monoxide (DLCO) was 60% and DLCO⁄alveolar volume (VA) 92% of predicted. Increased severity of restriction - based on TLC - was associated with lower DLCO (74% of predicted in mild restriction and 39% of predicted in severe restriction) and higher forced expiratory volume in 1 s (FEV1)⁄FVC ratio (82% of predicted in mild restriction and 90% of predicted in severe restriction) but not with age (76 years in mild restriction and 69 years in severe restriction). Regardless of severity of restriction, the average DLCO⁄VA (≥86% of predicted) remained within normal limits., Conclusions: One in four patients with IPF had normal TLC and more than one-half had a normal FVC during initial evaluation. As the severity of the restriction increased, FEV1⁄FVC increased, DLCO decreased but DLCO⁄VA remained normal.

Background: Approximately half of the world's population, and up to 90% of households in rural areas of developing countries, depend on biomass for cooking and heating., Setting: The National Institute of Respiratory Diseases, México City., Objective: To describe wood smoke-associated lung disease (WSLD)., Design: Description of the clinical, functional and radiological manifestations of patients with WSLD, and a comparison of pathological findings of patients who died of WSLD and smokers who died of chronic bronchitis., Results: All patients with WSLD were non-smoking women with chronic bronchitis, in whom asthma, bronchiectasis, tuberculosis, congestive heart failure, extreme obesity and alfa-1 antitrypsin deficiency had been excluded. All patients used wood for cooking and had been exposed to wood smoke for a median of 45 years. Dyspnoea, airway obstruction, air trapping, increased airway resistance, pathological evidence of anthracosis, chronic bronchitis, centrilobular emphysema and pulmonary hypertension were present in most patients with WSLD. Bronchial squamous metaplasia was a common finding. There were no significant differences in the histopathological findings between patients with WSLD and smokers. Diffuse interstitial fibrosis was absent in all patients., Conclusions: Patients with WSLD have obstructive lung disease, chronic bronchitis, emphysema and pulmonary hypertension comparable to smokers.