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Chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) is an important potential consequence of venous thromboembolic disease. Untreated CTEPD with pulmonary hypertension (CTEPH) is associated with high rates of morbidity and mortality. Several treatment options are now available for patients with CTEPD and CTEPH, including pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, medical therapy or a combination of therapies. Choice of treatment depends on the location of the thromboembolic disease burden, presence and severity of PH and patient factors, including frailty, parenchymal lung disease and other comorbidities. PEA is a complex surgery that can result in excellent outcomes and resolution of disease, but also comes with the risk of serious perioperative complications. This manuscript examines the history of PEA and its place in Australasia, and reports on outcomes from the main Australasian CTEPH expert centre. It provides a summary of up-to-date guidance on how PEA should be utilised in the overall management of these patients and describes opportunities and challenges for the future diagnosis and management of this disease, particularly in the Australasian setting.
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OBJECTIVES: Autoimmune disorders are multifactorial but occupational exposures have long been implicated, including respirable crystalline silica (RCS). A modern epidemic of silicosis is emerging internationally, associated with dry processing of engineered stone with high (>90%) RCS content. We aimed to investigate the prevalence of clinical autoimmune disease and common autoantibodies in exposed workers. METHODS: Stone benchtop industry workers in Victoria, Australia were offered free screening for silicosis and related disorders. Symptoms or diagnoses of autoimmune disease were evaluated by questionnaire and blood tests taken for rheumatoid factor (RF), antinuclear antibodies (ANAs) and extractable nuclear antigens (ENAs). RESULTS: Among 1238 workers (93.3% male) screened from 2019 to 2021, 0.9% were confirmed with autoimmune disease. Among those without clinical disease, 24.6% had detectable ANAs (93.5% male), 4.6% detectable ENAs and 2.6% were positive for RF. Silicosis was diagnosed in 253 workers (24.3% of those with diagnostic information available). Of those with ANA readings, 54 (6.6%) had ANA titre >1:320. The likelihood of positive autoantibodies increased with age; smoking; higher exposure to RCS and silicosis diagnosis. CONCLUSION: The proportion of workers with detectable ANAs or ENAs was considerably higher than the 5%-9% expected in the general population. Some of the antibodies detected (eg, Scl-70, CENPB) have high sensitivity and specificity for systemic sclerosis. Long-term follow-up will be needed to estimate incidence. Rheumatologists should explore occupational history in new cases of autoimmune disease. Screening for autoimmune disease is indicated in workers exposed to RCS as these individuals need specialised management and may be entitled to compensation.
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Autoanticuerpos , Enfermedades Autoinmunes , Exposición Profesional , Dióxido de Silicio , Silicosis , Humanos , Silicosis/epidemiología , Silicosis/inmunología , Silicosis/sangre , Silicosis/etiología , Masculino , Femenino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Adulto , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/inmunología , Autoanticuerpos/sangre , Dióxido de Silicio/efectos adversos , Victoria/epidemiología , Estudios de Cohortes , Anticuerpos Antinucleares/sangre , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/inmunología , Enfermedades Profesionales/sangre , Enfermedades Profesionales/etiología , Prevalencia , Anciano , Factor Reumatoide/sangre , Factor Reumatoide/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVE: Evidence for the benefit of steroid therapy in acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) is limited; however, they remain a cornerstone of management in other fibrotic interstitial lung diseases. This retrospective observational study assesses the effect of steroid treatment on in-hospital mortality in patients with acute exacerbation of fibrotic interstitial lung disease (AE-FILD) including IPF and non-IPF ILDs. METHODS: AE-FILD cases over a 10-year period were filtered using a code-based algorithm followed by individual case evaluation. Binary logistic regression analysis was used to assess the relationship between corticosteroid treatment (defined as ≥0.5 mg/kg/day of prednisolone-equivalent for ≥3 days within the first 72 h of admission) and in-hospital mortality or need for lung transplantation. Secondary outcomes included readmission, overall survival, requirement for domiciliary oxygen and rehabilitation. RESULTS: Across two centres a total of 107 AE-FILD subjects were included, of which 46 patients (43%) received acute steroid treatment. The steroid cohort was of younger age with fewer comorbidities but had higher oxygen requirements. Pre-admission FVC and DLCO, distribution of diagnoses and smoking history were similar. The mean steroid treatment dose was 4.59 mg/kg/day. Steroid use appeared to be associated with increased risk of inpatient mortality or transplantation (OR 4.11; 95% CI 1.00-16.83; p = 0.049). In the steroid group, there appeared to be a reduced risk of all-cause mortality in non-IPF patients (HR 0.21; 95% CI 0.04-0.96; p = 0.04) compared to their IPF counterparts. Median survival was reduced in the steroid group (221 vs. 520.5 days) with increased risk of all-cause mortality (HR 3.25; 95% CI 1.56-6.77; p < 0.01). CONCLUSION: In this two-centre retrospective study of 107 patients, AE-FILD demonstrates a high risk of mortality, at a level similar to that seen for AE-IPF, despite steroid treatment. Clinicians should consider other precipitating factors for exacerbations and use steroids judiciously. Further prospective trials are needed to determine the role of corticosteroids in AE-FILD.
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Progresión de la Enfermedad , Mortalidad Hospitalaria , Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/fisiopatología , Persona de Mediana Edad , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/mortalidad , Glucocorticoides/uso terapéutico , Resultado del Tratamiento , Prednisolona/uso terapéutico , Trasplante de PulmónRESUMEN
BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.
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Exposición Profesional , Radiografía Torácica , Sensibilidad y Especificidad , Silicosis , Tomografía Computarizada por Rayos X , Humanos , Silicosis/diagnóstico por imagen , Silicosis/etiología , Masculino , Adulto , Exposición Profesional/efectos adversos , Persona de Mediana Edad , Femenino , Enfermedades Profesionales/diagnóstico por imagen , Enfermedades Profesionales/etiología , Enfermedades Profesionales/diagnósticoRESUMEN
BACKGROUND: Lung cancer diagnosis, staging and treatment may be enhanced by multidisciplinary participation and presentation in multidisciplinary meetings (MDM). We performed a systematic review and meta-analysis to explore literature evidence of clinical impacts of MDM exposure. METHODS: A study protocol was registered (PROSPERO identifier CRD42021258069). Randomised controlled trials and observational cohort studies including adults with nonsmall cell lung cancer and who underwent MDM review, compared to no MDM, were included. MEDLINE, CENTRAL, Embase and ClinicalTrials.gov were searched on 31 May 2021. Studies were screened and extracted by two reviewers. Outcomes included time to diagnosis and treatment, histological confirmation, receipt of treatments, clinical trial participation, survival and quality of life. Risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomised Studies - of Interventions) tool. RESULTS: 2947 citations were identified, and 20 studies were included. MDM presentation significantly increased histological confirmation of diagnosis (OR 3.01, 95% CI 2.30-3.95; p<0.00001) and availability of clinical staging (OR 2.55, 95% CI 1.43-4.56; p=0.002). MDM presentation significantly increased likelihood of receipt of surgery (OR 2.01, 95% CI 1.29-3.12; p=0.002) and reduced the likelihood of receiving no active treatment (OR 0.32, 95% CI 0.21-0.50; p=0.01). MDM presentation was protective of both 1-year survival (OR 3.23, 95% CI 2.85-3.68; p<0.00001) and overall survival (hazard ratio 0.63, 95% CI 0.55-0.72; p<0.00001). DISCUSSION: MDM presentation was associated with increased likelihood of histological confirmation of diagnosis, documentation of clinical staging and receipt of surgery. Overall and 1-year survival was better in those presented to an MDM, although there was some clinical heterogeneity in participants and interventions delivered. Further research is required to determine the optimal method of MDM presentation, and address barriers to presentation.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Grupo de Atención al Paciente , Comunicación Interdisciplinaria , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
BACKGROUND: Many interstitial lung diseases (ILDs) have clear causal relationships with environmental and occupational exposures. Exposure identification can assist with diagnosis, understanding disease pathogenesis, prognostication and prevention of disease progression and occurrence in others at risk. Despite the importance of exposure identification in ILD, there is no standardised assessment approach. Many questionnaires are in clinical and research use, yet their utility, applicability, relevance and performance characteristics are unknown. OBJECTIVES: This scoping review aimed to summarise the available evidence relating to ILD exposure assessment questionnaires, identify research gaps and inform the content for a future single evidence-based ILD questionnaire. METHODS: A scoping review based on Arksey and O'Malley's methodological framework was conducted. ELIGIBILITY CRITERIA: Any questionnaire that elicited exposures specific to ILD was included. A modified COSMIN Risk of Bias Framework was used to assess quality. SOURCES OF EVIDENCE: Relevant articles were identified from MEDLINE and EMBASE up to 23 July 2023. RESULTS: 22 exposure questionnaires were identified, including 15 generally pertaining to ILD, along with several disease-specific questionnaires for hypersensitivity pneumonitis (n=4), chronic beryllium disease, sarcoidosis and silicosis (1 questionnaire each). For most questionnaires, quality was low, whereby the methods used to determine exposure inclusion and questionnaire validation were not reported or not performed. Collectively the questionnaires covered 158 unique exposures and at-risk occupations, most commonly birds, mould/water damage, wood dust, asbestos, farming, automotive mechanic and miners. Only five questionnaires also provided free-text fields, and 13 queried qualifiers such as temporality or respiratory protection. CONCLUSIONS: Designing a robust ILD-specific questionnaire should include an evidence-based and relevance-based approach to exposure derivation, with clinicians and patients involved in its development and tested to ensure relevance and feasibility.
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Enfermedades Pulmonares Intersticiales , Exposición Profesional , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Encuestas y Cuestionarios , Exposición Profesional/efectos adversos , Exposición a Riesgos Ambientales/efectos adversosAsunto(s)
Amianto , Mesotelioma Maligno , Mesotelioma , Enfermedades Profesionales , Exposición Profesional , Neoplasias Pleurales , Humanos , Mesotelioma/epidemiología , Mesotelioma/etiología , Enfermedades Profesionales/epidemiología , Sistema de Registros , Exposición Profesional/efectos adversos , Amianto/efectos adversosRESUMEN
Rationale: The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with mycophenolate. Methods: A literature search was conducted across the MEDLINE, EMBASE, and CENTRAL databases through June 2022 for studies using mycophenolate to treat patients with SSc-ILD. Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group method was used to assess the quality of evidence. Results: The literature review resulted in seven studies fitting the inclusion criteria. The systematic review and meta-analyses revealed changes in forced vital capacity % predicted (mean difference [MD], 5.4%; 95% confidence interval [95% CI]: 3.3%, 7.5%), diffusing capacity of the lung for carbon monoxide % predicted (MD, 4.64%; 95% CI: 0.54%, 8.74%), and breathlessness score (MD, 1.99; 95% CI: 0.36, 3.62) favored mycophenolate over placebo. The risk of anemia (relative risk [RR], 2.3; 95% CI: 1.2, 71.4) was higher with mycophenolate. There were no significant differences between mycophenolate and cyclophosphamide, except risk of premature discontinuation (RR, 0.6; 95% CI: 0.4, 0.9), and leukopenia (RR, 0.1; 95% CI: 0.05, 0.4) favored mycophenolate. The quality of evidence was moderate to very low per GRADE. Conclusions: Mycophenolate use in patients with SSc-ILD is associated with statistically significant improvements in disease progression and quality-of-life measures compared with placebo. There were no differences in mortality, disease progression, or quality of life compared with cyclophosphamide, but there were fewer adverse events. The quality of evidence is very low.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Calidad de Vida , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Ácido Micofenólico/uso terapéutico , Inmunosupresores/uso terapéutico , Ciclofosfamida/uso terapéutico , Pulmón , Progresión de la EnfermedadRESUMEN
Background: The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with cyclophosphamide. Data Sources: A literature search was conducted across the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using cyclophosphamide to treat patients with SSc-ILD. Data Extraction: Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group method was used to assess the quality of evidence. Synthesis: Five studies were included; two randomized controlled trials compared cyclophosphamide versus placebo, and one randomized controlled trial and two retrospective case-control studies compared cyclophosphamide versus mycophenolate. Compared with placebo, there was a 2.83% reduction in the decline at 12 months for forced vital capacity (FVC) % predicted using cyclophosphamide (95% confidence interval [CI], 0.80-4.87; low evidence). There were improvements in breathlessness (Transition Dyspnea Index mean difference [MD], 2.90; 95% CI, 1.94-3.86; minimum clinically important difference, 1; moderate evidence) and disability (Health Assessment Questionnaire-Disability Index MD, -0.16; 95% CI, -0.28 to -0.04; minimum clinically important difference, -0.14; moderate evidence). There were increased risks of leukopenia and constitutional symptoms using cyclophosphamide, but no difference in mortality. When cyclophosphamide was compared with mycophenolate, there were differences in diffusing capacity of the lung for carbon monoxide % predicted favoring mycophenolate at 6 months (MD, -3.67%; 95% CI, -6.3% to -1.1% unadjusted; MD, -4.88%; 95% CI, -7.3% to -2.5% adjusted for alveolar volume; moderate evidence), 12 months (MD, -5.90%; 95% CI, -8.4% to -3.4% adjusted for alveolar volume; moderate evidence), and 18 months (MD, -3.26%; 95% CI, -6.1% to -0.4%; moderate evidence), but not at 24 months. There were no differences in FVC % predicted, mortality, or quality-of-life outcomes, but participants were more likely to prematurely discontinue cyclophosphamide compared with mycophenolate (relative risk, 1.70; 95% CI, 1.10-2.63; high-certainty evidence). Conclusions: A review of the published evidence shows that cyclophosphamide is effective in SSc-ILD compared with placebo, with an increased risk of side effects. However, mycophenolate may be equivocal or better than cyclophosphamide. Clinicians and patients should weigh the potential benefits and risks with respect to individual patient circumstances and preferences.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Estudios Retrospectivos , Calidad de Vida , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Disnea/tratamiento farmacológico , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológicoRESUMEN
Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Estados Unidos , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Ciclofosfamida/uso terapéutico , Rituximab/uso terapéutico , Esclerodermia Sistémica/complicaciones , PulmónRESUMEN
Background: The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with rituximab. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through June 2022 for studies using rituximab to treat patients with SSc-ILD. Data Extraction: Disease progression, quality of life, mortality, and adverse event data were extracted. The intervention was rituximab. The standard-of-care comparator group was decided a priori by consensus of the panel as either placebo or mycophenolate. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Synthesis: Three relevant studies were selected. Rituximab significantly improved the forced vital capacity % predicted (mean difference, 3.13; 95% confidence interval [CI], 0.37 to 5.90) and the modified Rodnan Skin Score (mean difference, -7.01; 95% CI, 11.46 to -2.56) at 24-48 weeks. Conclusions: Rituximab use in patients with SSc-ILD is associated with stabilization of lung function. The quality of evidence for study outcomes was considered to be very low, as defined by the GRADE approach. Additional research on treatment with rituximab is imperative.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Calidad de Vida , Inmunosupresores/uso terapéutico , Esclerodermia Sistémica/tratamiento farmacológico , PulmónRESUMEN
Background: The American Thoracic Society convened an international multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with nintedanib alone or with the combination of nintedanib plus mycophenolate. Data Sources: Literature searches were conducted across MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using nintedanib or nintedanib plus mycophenolate to treat patients with SSc-ILD. Data Extraction: Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analysis was performed when possible. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group method was used to assess the quality of evidence. Synthesis: For nintedanib therapy alone, the systematic review included three total studies and revealed that disease progression was less in the nintedanib arm (the annual rate of decline in forced vital capacity [FVC] was 44.5 ml less, the absolute change from baseline was 46.4 ml less, and FVC% predicted was 1.2% less in the nintedanib arm) compared with placebo. However, gastrointestinal side effects and treatment discontinuation were double in the nintedanib arm compared with placebo. For combination therapy, the systematic review also included three total studies and revealed that changes in the annual rate of decline in FVC favored combination therapy over placebo (mean difference, 79.1 ml). Combination therapy was, however, associated with increased gastrointestinal adverse effects compared with placebo. The quality of evidence for all outcomes was very low as per GRADE. Conclusions: The use of nintedanib alone and in combination with mycophenolate in patients with SSc-ILD is associated with a significant reduction in disease progression compared with placebo but at the cost of increased gastrointestinal side effects and treatment discontinuation. The quality of evidence is very low.
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Indoles , Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Calidad de Vida , Inmunosupresores/uso terapéutico , Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Esclerodermia Sistémica/complicacionesRESUMEN
Background: The American Thoracic Society (ATS) convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Objective: To conduct a systematic review and evaluate the literature to determine the impact of treating patients with SSc-ILD with tocilizumab on prespecified critical and important outcomes determined by the ATS guideline panel. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through June 2022 for studies using tocilizumab to treat patients with SSc-ILD. Data Extraction: Mortality and disease progression were determined to be critical outcomes of focus, with quality of life and adverse events important outcomes. Data on these outcomes were extracted and meta-analyses performed using the generic inverse variance method when possible. The Grading of Recommendations, Assessment, Development, and Evaluation Working Group method was used to assess the quality of evidence. Synthesis: The literature review resulted in five studies for inclusion. The absolute decrease from baseline in forced vital capacity (FVC) for the tocilizumab arm was 118 ml, 241 ml, and 129 ml less than the placebo arm at 24, 48, and 96 weeks, respectively, favoring tocilizumab. The mean decrease in FVC% predicted at 48 weeks was 6.50% less and the risk of decrease >10% was 66% less in the tocilizumab arm, whereas patients were 1.97 times more likely to have any increase in FVC% predicted if they received tocilizumab in place of placebo. When the placebo arm was given tocilizumab from 48 to 96 weeks, the mean change in absolute FVC was 54.90 ml less and the mean change in FVC% predicted was 1.30% less. For diffusing capacity of the lung for carbon monoxide (DlCO)% predicted, at 48 weeks there was 1.50% less change and from 48 to 96 weeks there was 5.40% less change in the tocilizumab arm. Quantitative Interstitial Lung Disease scores and Quantitative Lung Fibrosis scores at 48 weeks and modified Rodnan skin scores at 72 weeks all favored the tocilizumab arm, as did several adverse event parameters, including serious adverse events (mean difference, -27.40; 95% confidence interval, -30.10 to -24.70). The quality of evidence was very low grade. Conclusions: Tocilizumab use in patients with SSc-ILD is associated with less disease progression and a better toxicity profile than placebo. However, the quality of evidence is very low, and large prospective studies dedicated to assessing tocilizumab specifically for SSc-ILD are needed.
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Anticuerpos Monoclonales Humanizados , Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Estudios Prospectivos , Calidad de Vida , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Pulmón , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Capacidad Vital , Progresión de la EnfermedadRESUMEN
PURPOSE OF REVIEW: There has been a rapid increase in silicosis cases, particularly related to artificial stone. The key to management is avoidance of silica exposure. Despite this, many develop progressive disease and there are no routinely recommended treatments. This review provides a summary of the literature pertaining to pharmacological therapies for silicosis and examines the plausibility of success of such treatments given the disease pathogenesis. RECENT FINDINGS: In-vitro and in-vivo models demonstrate potential efficacy for drugs, which target inflammasomes, cytokines, effector cells, fibrosis, autophagy, and oxidation. SUMMARY: There is some evidence for potential therapeutic targets in silicosis but limited translation into human studies. Treatment of silicosis likely requires a multimodal approach, and there is considerable cross-talk between pathways; agents that modulate both inflammation, fibrosis, autophagy, and ROS production are likely to be most efficacious.
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Dióxido de Silicio , Silicosis , Humanos , Fibrosis , Autofagia , CitocinasRESUMEN
BACKGROUND: Optimizing donor use and achieving maximal survival following lung transplantation (LTx) require a pretransplant assessment that identifies clinical, physiological, and psychosocial patient factors associated with both poor and optimal post-LTx survival. We examined the utility of a psychosocial tool, the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT), to identify patient suitability for LTx, as well as its association with clinical outcomes before and after LTx. METHODS: This was a retrospective single-center study analyzing LTx assessment clinical variables (age, gender, diagnosis, functional capacity, nutrition, renal function), with a particular focus on the utility of the SIPAT score, to predict patient suitability for LTx. The same variables were analyzed against LTx waitlist mortality, as well as post-LTx survival. RESULTS: Over an 8-year period dating from December 2012, 914 patients (male 54.4%, mean age 55.2 years) underwent LTx assessment. Patients declined for LTx (n = 152, 16.6%) were older and had reduced functional capacity, nutritional markers, and renal function but had a higher SIPAT score. Once listed for LTx, a higher SIPAT score was not associated with waitlist mortality or reduced post-LTx survival. CONCLUSIONS: The SIPAT tool measures psychosocial suitability for transplantation that can be incorporated into a standardized assessment of LTx suitability. While patients with higher SIPAT score were more likely to be declined for LTx, the SIPAT score did not predict outcome in transplanted patients. A subgroup of patients with high SIPAT scores were successfully transplanted, suggesting that unfavorable psychosocial variables are potentially modifiable with a well-resourced multidisciplinary LTx team.
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Trasplante de Pulmón , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Occupational exposures are directly causal or partially contributory to the development of interstitial lung diseases. A detailed occupational history, relevant high-resolution computed tomography findings, and where relevant additional histopathology, are required to make a diagnosis. Treatment options are limited, and further exposure avoidance is likely to reduce disease progression.
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Alveolitis Alérgica Extrínseca , Enfermedades Pulmonares Intersticiales , Enfermedades Profesionales , Exposición Profesional , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Profesionales/complicaciones , Enfermedades Profesionales/diagnóstico , Exposición Profesional/efectos adversos , Tomografía Computarizada por Rayos X , Pulmón , Alveolitis Alérgica Extrínseca/diagnóstico , Alveolitis Alérgica Extrínseca/etiologíaRESUMEN
Challenges for the effective management of interstitial lung diseases (ILDs) include difficulties with the early detection of disease, accurate prognostication with baseline data, and accurate and precise response to therapy. The purpose of this Review is to describe the clinical and research gaps in the diagnosis and prognosis of ILD, and how machine learning can be applied to image biomarker research to close these gaps. Machine-learning algorithms can identify ILD in at-risk populations, predict the extent of lung fibrosis, correlate radiological abnormalities with lung function decline, and be used as endpoints in treatment trials, exemplifying how this technology can be used in care for people with ILD. Advances in image processing and analysis provide further opportunities to use machine learning that incorporates deep-learning-based image analysis and radiomics. Collaboration and consistency are required to develop optimal algorithms, and candidate radiological biomarkers should be validated against appropriate predictors of disease outcomes.
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Enfermedades Pulmonares Intersticiales , Radiología , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/terapia , Pronóstico , Factores de Riesgo , BiomarcadoresRESUMEN
BACKGROUND AND OBJECTIVE: Identification of an exposure is integral to the diagnosis, management, and prognostication of chronic hypersensitivity pneumonitis (CHP). Standardized questionnaires may aid in the identification of exposures, however, there currently are no evidence-based patient-validated questionnaires available. Key qualifiers (including duration and frequency) which indicate exposure relevance are also poorly defined. This study assessed the use of a standardized CHP exposure questionnaire in the identification of exposures and diagnostic confidence of CHP. METHODS: People with a multi-disciplinary meeting (MDM) diagnosis from five Australian interstitial lung disease (ILD) expert centres who provided informed consent were included. Participants completed a previously developed standardized CHP Exposure Questionnaire. Responses were collected with the participant's MDM data, including diagnosis, diagnostic confidence, and clinician-elicited exposures. RESULTS: One hundred thirty participants (IPF = 58, CHP = 24, CTD-ILD = 17, unclassifiable = 19, other = 12) were included. In 33% of CHP participants, a standardized questionnaire elicited an exposure where the clinician did not. 63% of these had provisional low confidence CHP; and an exposure history would have increased the diagnostic confidence in these cases. Using the standardized questionnaire, 96% of CHP participants reporting any exposure, compared with 75% of non-HP ILD participants. CHP participants were 3.5 times more likely (p = 0.004) to report their symptoms improved on avoidance, and 2.3 times more likely (p = 0.018) to report daily frequent exposure, compared with non-HP ILDs. CONCLUSION: A standardized questionnaire which elicits exposure characteristics in addition to presence or absence of relevant exposures can increase the diagnostic confidence of CHP and reduce the proportion of antigen-indeterminate CHP.
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Alveolitis Alérgica Extrínseca , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedad Crónica , Australia , Alveolitis Alérgica Extrínseca/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Encuestas y CuestionariosRESUMEN
Background: Identification of potential inciting antigens known to be associated with hypersensitivity pneumonitis (HP) is integral to achieving a confident diagnosis, its management, and prognostication. A barrier to achieving diagnostic confidence is that evidence for exposure assessment is not presented in an easily accessible or useful format. Objective: To develop a freely available comprehensive living repository of contemporaneous exposures associated with HP. Methods: Electronic searches were performed through Medline, Embase, and Web of Science from January 1, 2002, to December 31, 2019, using the following broad MeSH headings: ([allerg* or hypersensitiv*], and adj [alveol* or pneumo*]).mp. Articles were included if they described adults or children with a diagnosis of HP (as defined by authors) and a description of the causative exposure. Website development used a structured query language database and was powered by WordPress. Results: HPLung.com is a freely available online searchable repository that lists all exposures and antigens associated with HP and links to their parent studies. Eighty-five unique exposures from 447 citations have been included thus far. The website continues to be updated iteratively. Since its launch in 2019, HPLung.com has been visited over 4,500 times by users from 75 different countries. Conclusion: HPLung.com is a novel knowledge-sharing tool that addresses barriers of accessibility, contemporaneity, efficient evidence synthesis, and making the best use of technological platforms to improve the exposure assessment of those suspected of HP.
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OBJECTIVE: The aim of this study was to compare patients' preferred role in medical decision-making before the initial urogynecology visit to their perceived role after the visit. METHODS: This prospective cohort study enrolled women presenting for their initial urogynecology visit. Before and after the visit, patients completed the Control Preference Scale (CPS), which categorizes the role that patients want to have in medical decision-making: active, collaborative, or passive. Patients also completed the Pelvic Floor Distress Inventory, CollaboRATE, Patient Global Impression of Improvement, patient satisfaction, and Short Test of Functional Health Literacy in Adults questionnaires. Univariable and multivariable generalized estimating equations were used. RESULTS: Women (n = 100) with a mean age of 59.1 years (SD = 15.5) participated in the study. Based on CPS before the visit, 50% of the women preferred active involvement, whereas 45% preferred collaborative and 5% preferred passive involvement. After the visit, these rates change to 40%, 48%, and 11%, respectively. On univariable analysis, women were 1.56 times more likely to report a collaborative or passive CPS response after the visit (P = 0.02). This remained true on multivariable analysis (odds ratio, 1.57; P = 0.04). Patients' CPS responses were not associated with their responses on CollaboRATE, Patient Global Impression of Improvement, patient satisfaction, or Short Test of Functional Health Literacy in Adults. Eighty-eight percent of women reported a fully collaborative visit based on CollaboRATE, and 87% reported being "completely satisfied" with the visit. CONCLUSIONS: Despite a change in women's reported involvement in decision-making after their first urogynecology visit compared with their preferences before the visit, most women perceived collaboration during their visit and were completely satisfied.