Clinical course of suspected familial and sporadic idiopathic pulmonary fibrosis: Data from the PROOF-Next registry.

BACKGROUND AND OBJECTIVE: Real-life data on suspected familial fibrosis, defined as the occurrence of the disease in a patient younger than 50 and/or having at least one relative affected by pulmonary fibrosis remain scarce. METHODS: The Belgian and Luxembourg IPF registry (PROOF-Next) is a multicentric prospective longitudinal and observational study set in Belgium and Luxembourg. We compared characteristics and clinical course of patients with suspected familial pulmonary fibrosis (FPF) and sporadic IPF. RESULTS: We included 618 patients in the analysis, of whom 76 (12%) fulfilled criteria for FPF. They were significantly younger than sIPF (median age (range) 65 (43-87), vs. 72 (51-98), p = 0.0001). Male gender proportion and smoking status did not differ between groups, but the number of pack-year among current and former smokers was lower in FPF (20 vs. 25, p = 0.02). Besides, 87% of FPF and 76% of sIPF were treated with antifibrotic (p = 0.047). Baseline pulmonary function tests were similar in both groups, as well as median time before progression and transplant-free survival. Finally, genetic testing, performed in a minority, led to the identification of 10 telomerase-related gene variants. CONCLUSION: Although younger and exposed to less tobacco, patients with FPF show an equally aggressive progression as observed in sporadic IPF patients. These results warrant early referral of FPF patients to expert centres for optimal management.

Thoracic Society of Australia and New Zealand clinical practice guideline on adult home oxygen therapy.

This Thoracic Society of Australia and New Zealand Guideline on the provision of home oxygen therapy in adults updates a previous Guideline from 2015. The Guideline is based upon a systematic review and meta-analysis of literature to September 2022 and the strength of recommendations is based on GRADE methodology. Long-term oxygen therapy (LTOT) is recommended for its mortality benefit for patients with COPD and other chronic respiratory diseases who have consistent evidence of significant hypoxaemia at rest (PaO2 ≤ 55 mm Hg or PaO2 ≤59 mm Hg in the presence of hypoxaemic sequalae) while in a stable state. Evidence does not support the use of LTOT for patients with COPD who have moderate hypoxaemia or isolated nocturnal hypoxaemia. In the absence of hypoxaemia, there is no evidence that oxygen provides greater palliation of breathlessness than air. Evidence does not support the use of supplemental oxygen therapy during pulmonary rehabilitation in those with COPD and exertional desaturation but normal resting arterial blood gases. Both positive and negative effects of LTOT have been described, including on quality of life. Education about how and when to use oxygen therapy in order to maximize its benefits, including the use of different delivery devices, expectations and limitations of therapy and information about hazards and risks associated with its use are key when embarking upon this treatment.

Retrospective review comparing intrapleural fibrinolytic therapy (alteplase) and surgical intervention in complex pleural effusion.

BACKGROUND: Intrapleural fibrinolytic therapy (IPFT) is one of the treatment options for complex pleural effusion. In this study, the IPFT agent used was alteplase, a tissue plasminogen activator (t-PA). This study aims to determine the difference in the outcome of patients with complex pleural effusion between IPFT and surgery in terms of radiological improvement, inflammatory parameters, length of stay, and post-intervention complications. METHODS: A retrospective review of patients with complex pleural effusion treated at Universiti Kebangsaan Malaysia Medical Center from January 2012 to August 2020 was performed. Patient demographics, chest imaging, drainage chart, inflammatory parameters, length of hospital stay, and post-intervention and outcome were analyzed. RESULTS: Fifty-eight patients were identified (surgical intervention, n = 18; 31% and IPFT, n = 40, 69%). The mean age was 51.7 ± 18.2 years. Indication for surgical intervention was pleural infection (n = 18; 100%), and MPE (n = 0). Indications for IPFT was pleural infection (n = 30; 75%) and MPE (n = 10; 25%). The dosages of t-PA were one to five doses of 2-50 mg. The baseline chest radiograph in the IPFT group was worse than in the surgical intervention group. (119.96 ± 56.05 vs. 78.19 ± 55.6; p = 0.029) At week 1, the radiological success rate for IPFT and surgical intervention were 27% and 20%, respectively, and at weeks 4-8, the success rate was 56% and 80% respectively. IPFT was associated with lesser complications; fever (17.5%), chest pain (10%), and non-life-threatening bleeding (5%). CONCLUSION: IPFT was comparable to surgery in radiological outcome, inflammatory parameters, and length of stay with lesser reported complications.

Opportunities to diagnose fibrotic lung diseases in routine care: A primary care cohort study.

BACKGROUND AND OBJECTIVE: Temporal trends of healthcare use in the period before a diagnosis of pulmonary fibrosis are poorly understood. We investigated trends in respiratory symptoms and LR HRU in the 10 years prior to diagnosis. METHODS: We analysed a primary care clinical cohort database (UK OPCRD) and assessed patients aged ≥40 years who had an electronically coded diagnosis of pulmonary fibrosis between 2005 and 2015 and a minimum 2 years of continuous medical records prior to diagnosis. Exclusion criteria consisted of electronic codes for recognized causes of pulmonary fibrosis such as CTD, sarcoidosis or EAA. RESULTS: Data for 2223 patients were assessed. Over the 10 years prior to diagnosis of pulmonary fibrosis, there was a progressive increase in HRU across multiple LR-related domains. Five years before diagnosis, 18% of patients had multiple healthcare contacts for LR complaints; this increased to 79% in the year before diagnosis, with 38% of patients having five or more healthcare contacts. CONCLUSION: There are opportunities to diagnose pulmonary fibrosis at an earlier stage; research into case-finding algorithms and strategies to educate primary care physicians is required.

Corticosteroid use is not associated with improved outcomes in acute exacerbation of IPF.

BACKGROUND AND OBJECTIVE: AE-IPF has profound prognostic implications, preceding approximately half of all IPF-related deaths. Despite this clinical significance, there are limited data to guide management decisions. Corticosteroids remain the mainstay of treatment despite a lack of strong supporting evidence and mounting concern that they may be harmful. We assessed the impact of corticosteroid therapy on in-hospital mortality in AE-IPF patients. METHODS: AE-IPF subjects were retrospectively identified in the UCSF medical centre's electronic health records from 1 January 2010 to 1 August 2018 using a code-based algorithm followed by case validation. The relationship between corticosteroid treatment and in-hospital mortality was assessed using a Cox model and a propensity score to control for confounding by indication. Secondary outcomes included hospital readmissions and overall survival. RESULTS: In total, 82 AE-IPF subjects were identified, of whom 37 patients (45%) received corticosteroids. AE-IPF subjects treated with corticosteroids were more likely to require ICU level care and mechanical ventilation. There was no statistically significant association between corticosteroid treatment and in-hospital mortality (propensity score weighted, adjusted HR: 1.31; 95% CI: 0.26-6.55; P = 0.74). Overall survival was reduced in AE-IPF subjects receiving corticosteroids (HR: 6.17; 95% CI: 1.35-28.14; P = 0.019). CONCLUSION: Our study found no evidence that corticosteroid use improves outcomes in IPF patients admitted to the hospital with acute exacerbation. Furthermore, corticosteroid use may contribute to reduced overall survival following an exacerbation. Observational cohort studies using larger real-world cohorts can more definitively assess the relationship between corticosteroid treatment and short-term outcomes in AE-IPF.

Acute exacerbations of fibrotic interstitial lung diseases.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) is a severe complication of idiopathic pulmonary fibrosis (AE-IPF). In 2016, an international working group revised its definition and diagnostic criteria; however, few studies have assessed the frequency and prognosis of AE in patients with other fibrotic interstitial lung diseases (FILD). METHODS: We used data from 1019 consecutive interstitial lung disease (ILD) patients initially evaluated between January 2008 and July 2015. All subject diagnoses were made by multidisciplinary discussion in December 2018. ILD was categorized as IPF (n = 462) and other FILD which included non-specific interstitial pneumonia (n = 22), chronic hypersensitivity pneumonitis (n = 29), connective tissue disease-associated ILD (n = 205) and unclassifiable ILD (n = 209). Using the 2016 definition of AE-IPF, we identified all subjects with an AE. RESULTS: During the observational period, 193 patients experienced a first AE (AE-FILD n = 69, AE-IPF n = 124). The time to first AE was significantly longer in FILD than IPF (log-rank test, P < 0.001). After adjusting for potentially influential confounders, FILD remained a significant predictor of longer time to first AE compared with IPF (hazard ratio: 0.453; 95% CI: 0.317-0.647, P = 0.006). In a multivariate Cox proportional analysis, baseline disease severity was closely associated with the incidence of AE-ILD. Even after adjustment for other clinical variables, AE had a negative impact on overall survival. AE-FILD and AE-IPF showed similar poor short-term outcomes. CONCLUSION: All forms of ILD are at risk of AE and have a similar outcome to AE-IPF.

Serum prednisolone levels as a marker of oral corticosteroid adherence in severe asthma.

BACKGROUND: Severe asthma is a complex heterogeneous disease typically requiring advanced therapies. Underlying the treatment of all asthma, however, is the consistent recommendation across international guidelines to ensure that adherence to therapy is adequate. Currently, there is no consensus on an objective marker of adherence. METHODS: We performed a prospective observational study of 17 participants taking oral prednisolone using serum prednisolone levels as a marker of adherence, and sputum eosinophilia as a marker of control of type 2 airway inflammation. Based on these biomarkers, we classified participants into a non-adherent and an adherent cohort, and further stratified by the presence of ongoing sputum eosinophilia. RESULTS: We identified 3 non-adherent participants and 14 who were adherent, based on their serum prednisolone levels. Stratification using sputum eosinophil counts identified one participant as having ongoing sputum eosinophilia in the setting of non-adherence, while six were identified as steroid resistant with ongoing sputum eosinophilia despite adherence to oral prednisolone therapy. CONCLUSION: Serum prednisolone can be used an objective marker of adherence in those patients with severe asthma taking daily oral prednisolone. In combination with sputum eosinophil counts, a steroid resistant cohort can be distinguished from one with ongoing inflammation in the setting of non-adherence. This information can then be used by clinicians to differentiate the optimal next steps for treatment in these specific populations. TRIAL REGISTRATION: Participants were recruited as part of the Markers of Inflammation in the Management of Severe Asthma (MIMOSA) study, trial registration ACTRN12616001015437 , 02 August 2016.

Rehabilitation in chronic respiratory diseases: In-hospital and post-exacerbation pulmonary rehabilitation.

Exacerbations of chronic obstructive pulmonary disease (COPD) that require hospitalization are important events for patients. Functional impairment and skeletal muscle dysfunction can increase the risk of hospitalization and readmission, independent of lung function. In addition, once a patient is admitted, multiple factors can lead to worsening outcome including immobility, systemic inflammation and nutritional depletion. These non-pulmonary factors are potentially amenable to exercise therapy, as part of pulmonary rehabilitation (PR). Peri-exacerbation PR has an important role in the management of exacerbations of COPD. In this review, we explore how functional limitation and skeletal muscle dysfunction affect patients having a severe exacerbation of COPD, the systemic impact of hospitalization on patients including potential aetiologies and the role of PR around the time of an exacerbation. This includes rehabilitation during the inpatient phase, post-exacerbation rehabilitation and rehabilitation bridging hospital discharge. We also describe potential future developments in peri-exacerbation PR.

Recombinant thrombomodulin for acute exacerbation in idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) or other idiopathic interstitial pneumonias (IIP) is a poor prognostic event despite conventional therapy with corticosteroids and/or immunosuppressants. We aimed to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhTM) for AE-IIP. METHODS: For this prospective single-arm open-label multicentre cohort study, we retrospectively registered 61 cases of AE-IIP treated with conventional therapy between 2011 and 2013 (control arm), and prospectively enrolled 39 cases of AE-IIP treated with conventional therapy and rhTM (380 U/kg/day for 6 days) between 2014 and 2016 (rhTM arm). To reduce potential confounding in treatment comparisons, an adjusted mortality analysis for 90-day survival was conducted with weighted Cox proportional hazards regression models using inverse probability of treatment weighting. Weights were derived from propensity scores estimated using a multivariable logistic regression analysis including potential confounders. RESULTS: The 90-day survival rates of AE-IIP patients treated with/without rhTM were 66.7% (26/39) and 47.5% (29/61), respectively. After adjusting for imbalances, rhTM therapy was significantly associated with reduced mortality (adjusted hazard ratio (HR): 0.453; 95% CI: 0.237-0.864; P = 0.0163). The frequencies of adverse events with/without rhTM were 17.9% (7/39) and 19.7% (12/61), which were similar in both arms (P = 1.0). Two bleeding-related adverse events occurred in the rhTM arm. CONCLUSION: Safety and efficacy were observed for rhTM treatment of AE-IIP. A future randomized controlled trial is required to draw final conclusions.

Prevalence and nature of lung function abnormalities among Indigenous Australians referred to specialist respiratory outreach clinics in the Northern Territory.

BACKGROUND: Poor lung function is a predictor of future all-cause mortality. In Australia, respiratory diseases are particularly prevalent among the indigenous population, especially in remote communities. However, there are little published pulmonary function tests' (PFT) data of remote-based adult indigenous patients. AIM: To evaluate the severity of airflow obstruction and other PFT abnormalities of adults referred to specialist respiratory clinics in remote indigenous communities. METHODS: Retrospective analysis of PFT (pre- and post-bronchodilator spirometry, total lung capacity (TLC) and diffusing capacity to carbon monoxide (DLCO)) of indigenous patients collected during specialist respiratory clinics in remote Northern Territory (NT) indigenous communities (Australia) between 2013 and 2015. The National Health and Nutrition Examination Survey (NHANES) III without ethnic correction was used as the reference. RESULTS: Of the 357 patients, 150 had acceptable spirometry, and 71 had acceptable DLCO and TLC studies. Despite the relatively young age (mean = 49 years, SD = 12.9), their lung function was generally low; mean % predicted values were FEV1 = 55% (SD = 20.5%), FVC = 61% (SD = 15.6%), DLCO = 64.0% (SD = 19.7%) and TLC = 70.1% (SD = 18.2%). Mean FEV1 /FVC ratio was preserved (0.71, SD = 0.16). Post-bronchodilator airflow obstruction (FEV1 /FVC < 0.7) was observed in 37% of patients, where a large proportion (67%) demonstrated at least a severe airflow obstruction, with a mean FEV1 of 41% predicted. CONCLUSION: In this first study of PFT findings of indigenous adults from a remote-based clinical service, we found a high rate of at least moderate airflow limitation and low FVC along with preserved FEV1/FVC ratio. Increased awareness and screening for reduced lung function needs to be considered in this population.

Individualized breathlessness interventions may improve outcomes in patients with advanced COPD.

BACKGROUND AND OBJECTIVE: Many patients with advanced COPD experience refractory breathlessness and individualized breathlessness interventions may improve management of this complex symptom. The aims of this study were to develop, implement and assess the efficacy of a breathlessness intervention for patients with COPD and refractory breathlessness and to evaluate patient acceptability. METHODS: An individualized breathlessness plan, information leaflets, breathlessness education and a hand-held fan were offered to consecutive patients with severe COPD and refractory breathlessness attending a tertiary integrated respiratory and palliative care service. Validated dyspnoea, quality of life and anxiety/depression questionnaires were administered at baseline and after 6 weeks, with change in dyspnoea scores being the primary outcome measure. A subset of patients participated in a structured telephone interview to qualitatively assess the intervention. RESULTS: Twenty-six patients with severe COPD (mean forced expiratory volume in 1 s (FEV1 ) 38%) were included, with a mean age of 74 years. Mean modified Medical Research Council Breathlessness Scale score was 3.5. Anxiety and depression were common, being present in 38% and 35% of participants. At 6 weeks, there was a clinically significant improvement in breathlessness severity as measured by the Numerical Rating Scale. The subset of patients with anxiety/depression also saw significant improvement in all domains of the Self-Administered Standardized Chronic Respiratory Questionnaire (CRQ-SAS). Patients reported that the intervention was highly useful and acceptable. CONCLUSION: This feasibility study of individualized breathlessness interventions in patients with severe COPD and refractory breathlessness is the first to demonstrate a clinically significant reduction in dyspnoea scores, with high levels of patient acceptability.

Development and validation of a prognostic scoring model for Mycobacterium avium complex lung disease: an observational cohort study.

BACKGROUND: Patients with Mycobacterium avium complex (MAC) lung disease (LD) have a heterogeneous prognosis. This study aimed to develop and validate a prognostic scoring model for these patients using independent risk factors for survival. METHODS: We retrospectively analyzed the data of patients with MAC-LD from two hospitals (cohort 1, n = 368; cohort 2, n = 118). Cohort 1 was evaluated using a multivariate Cox proportional hazards model to identify independent risk factors for overall survival (OS). A prognostic scoring model composed of these factors was developed, and cohort 1 was stratified into three groups according to risk using the log-rank test. Finally, the prognostic scoring model was validated using the data of cohort 2. RESULTS: Seven independent risk factors for OS were selected from cohort 1, including the male sex, age ≥ 70 years, the presence of a malignancy, body mass index <18.5 kg/m2, lymphocyte count <1000 cells/µL, serum albumin levels <3.5 g/dL, and fibrocavitary disease. The areas under the receiver operating characteristic curves for the prognostic scoring model were 0.84 [95% confidence interval (CI), 0.80 - 0.89] for cohort 1 and 0.84 (95% CI, 0.75 - 0.92) for cohort 2. The 5-year OS rates of patients stratified into low-risk, intermediate-risk, and high-risk groups were 97.6, 76.6, and 30.8%, respectively (P < 0.001), in cohort 1, and 97.2, 82.3, and 45.4%, respectively (P < 0.001), in cohort 2. CONCLUSIONS: This study is the first to develop and validate a prognostic scoring model for patients with MAC-LD. This model may prove useful in clinical settings and practical in estimating the prognosis.

Treatment delay and fatal outcomes of pulmonary tuberculosis in advanced age: a retrospective nationwide cohort study.

BACKGROUND AND OBJECTIVE: Studies focusing on pulmonary tuberculosis in advanced age (≥80 years) are lacking. This study aimed to explore treatment delay, outcomes and their predictors in this group. METHODS: Adult (≥20 years) patients with pulmonary tuberculosis were identified from the National Health Insurance Research Database of Taiwan from 2004 to 2009. Treatment completion and mortality rates were noted at one year after treatment. RESULTS: Among the 81,081 patients with pulmonary tuberculosis identified, 13,923 (17.2%) were aged ≥80 years, and 26,897 (33.2%) were aged 65-79 years. The treatment completion, mortality rates and treatment delay were 54.8%, 34.7% and 61 (12-128) [median, (1st-3rd quartiles)] days in patients aged ≥80 years, 68.3%, 18.5% and 53 (8-122) days in patients aged 65-79 years, and 78.9%, 6.5% and 21 (1-84) days in patients aged <65 years, respectively. The elder patients were more likely to receive second-line anti-tuberculosis agents. The treatment completion rate decreased with older age, female sex, comorbidities, low income, requiring second-line anti-tuberculosis agents, severity of pulmonary tuberculosis and longer treatment delay. Older age, female sex, comorbidities, low income, and not undergoing rapid molecular diagnostic tests were independently associated with longer treatment delays. CONCLUSIONS: Pulmonary tuberculosis in advanced age has a longer treatment delay and a higher mortality rate. Applying rapid molecular diagnostic tools may reduce treatment delay and should be integrated into the diagnostic algorithm for pulmonary tuberculosis, particularly in elderly patients.

The interstitial lung disease multidisciplinary meeting: A position statement from the Thoracic Society of Australia and New Zealand and the Lung Foundation Australia.

Interstitial lung diseases (ILD) are a diverse group of pulmonary diseases for which accurate diagnosis is critical for optimal treatment outcomes. Diagnosis of ILD can be challenging and a multidisciplinary approach is recommended in international guidelines. The purpose of this position paper is to review the evidence for the use of the multidisciplinary meeting (MDM) in ILD and suggest an approach to its governance and constitution, in an attempt to provide a standard methodology that could be applied across Australia and New Zealand. This position paper is endorsed by the Thoracic Society of Australia and New Zealand (TSANZ) and the Lung Foundation Australia (LFA).