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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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Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Estados Unidos , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Ciclofosfamida/uso terapêutico , Rituximab/uso terapêutico , Escleroderma Sistêmico/complicações , PulmãoRESUMO
Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.
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Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Antiácidos/uso terapêutico , Biópsia , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/terapia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Estados UnidosRESUMO
Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited.Target Audience: Patients with COPD, clinicians who care for them, and policy makers.Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.Recommendations:1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.
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Hipercapnia/terapia , Ventilação não Invasiva/normas , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Crônica , Humanos , Hipercapnia/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores de TempoRESUMO
Asthma, chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are the most common respiratory disorders worldwide. Given demographic and environmental changes, prevalence for each is likely to increase. Although exact numbers are not known, based on chance alone, many people will be affected by both lower airways obstruction and concomitant upper airway obstruction during sleep. Some recent studies suggest that there is a reciprocal interaction, with chronic lung disease predisposing to OSA, and OSA worsening control and outcomes from chronic lung disease. Thus, the combination of wake and sleep respiratory disorders can create an overlap syndrome with unique pathophysiological, diagnostic and therapeutic concerns. Although much work needs to be done, given the above, Respirologists, Sleep Medicine and Primary Care providers must be vigilant for overlap syndromes. Accurate diagnosis of, for example, OSA as a cause of nocturnal symptoms in a patient with asthma is likely to limit further ineffective titration of medications for asthma. Moreover, prompt treatment of OSA in the overlap syndromes will not only offer symptomatic benefit of OSA, but also improve symptoms and healthcare resource utilization attributable to obstructive lung disease, and in COPD, it may reduce mortality.
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Asma/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Asma/tratamento farmacológico , Asma/fisiopatologia , Comorbidade , Humanos , Prevalência , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapiaRESUMO
Traditional, outpatient pulmonary rehabilitation provided to stable COPD patients leads to significant improvements in dyspnea, exercise capacity and health related quality of life. Also, when started during or shortly after a hospitalization for a COPD exacerbation, pulmonary rehabilitation improves these patient-centered outcomes and arguably reduces subsequent health care utilization and mortality. Despite these benefits, the uptake of traditional pulmonary rehabilitation remains disappointingly poor. Home-based pulmonary rehabilitation, a safe and effective alternative to traditional, center-based programs, can broaden access. While proven improvements in dyspnea, exercise capacity and health status justify implementation of home-based pulmonary rehabilitation, it would be helpful to know whether it can also decrease health care utilization and be cost-effective.
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Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitalização/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/reabilitação , Idoso , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Prestação Integrada de Cuidados de Saúde/normas , Progressão da Doença , Dispneia/etiologia , Dispneia/reabilitação , Tolerância ao Exercício/fisiologia , Nível de Saúde , Humanos , Mortalidade , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Qualidade de Vida/psicologia , Resultado do TratamentoRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder resulting in a myriad of adverse vascular risks, including altered inflammatory/anti-inflammatory adipokine balance. Recent studies are yet to agree on how this balance responds to the OSA severity. As it is customary in these studies to obtain a single blood sample in participants after completion of the nocturnal polysomnogram (PSG), we hypothesized that these adipokines' early ultradian pulsatility might contribute to the reported contradictory results. METHODS: Fasting serum leptin and adiponectin were measured every 15 minutes for one hour in the morning after the diagnostic PSG for 13 adults recruited consecutively from the Salem VAMC Sleep Clinic between September 2006 and October 2007. RESULTS: No differences in the timed paired samples of leptin (P = 0.30) and adiponectin (P = 0.28) were found in OSA participants (mean apnea-hypopnea index 21.1). CONCLUSION: Customary protocol of obtaining a single blood sample for leptin and adiponectin after nocturnal PSG seems appropriate.
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Adiponectina/sangue , Ritmo Circadiano/fisiologia , Leptina/sangue , Apneia Obstrutiva do Sono/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: The term "Overlap Syndrome" (OS) describes the presence of both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in a single individual. Excessive daytime sleepiness (EDS) is a common symptom of OS shown to be associated with an increased risk of cardiovascular disease (CVD) that could be reduced through exercise. Thus, we propose to investigate a novel exercise intervention in individuals with the EDS-OS phenotype as they are at highest risk of CVD yet have the greatest barriers to exercise. METHODS: We will conduct a single-site, randomized, two-arm, parallel group-controlled exercise trial in individuals with EDS-OS. The Epworth Sleepiness Scale (ESS) will be assessed at baseline. Individuals with OS and the EDS-OS phenotype (ESS >10) (n = 46) will be randomized to a moderate intensity interval training (MIIT, i.e. intervals of 5 min at 50% VO2peak followed by 3 min of active recovery at 10% VO2peak) or a control group of standard of care. We will investigate if MIIT intervention decreases the risk of CVD in EDS-OS, which will be assessed by: 1) quality of life, measured by the 36-Item Short Form Health Survey; 2) physical activity, measured by daily step counts; and 3) cardiovascular health, assessed as VO2peak, flow-mediated dilation and serum high sensitivity C-reactive protein, lipids, and glucose. CONCLUSION: Our findings will guide future development and implementation of exercise interventions that could reduce the risk of CVD in the understudied EDS-OS phenotype.
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Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Overlap Syndrome (OS), the co-occurrence of Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease. Clustering of patients in subgroups with similar pre-clinical manifestations (ie, endothelial dysfunction) may identify relevant therapeutic phenotype categories for patients with OS who are at high risk of CVD. We therefore conducted a cross-sectional pilot study of endothelial function in 7 patients with OS (Forced Expiratory Volume in 1 second/Forced Vital Capacity < 0.7) on continuous positive airway pressure therapy (n = 7) to assess the relationship between FMD and physical activity. We found a strong association between FMD and step counts (rho = 0.77, p = 0.04); and FMD and moderate physical activity (rho = 0.9, p = 0.005). Further, larger studies are needed to confirm that FMD may identify patients with OS at high risk of CVD who benefit from increased physical activity.
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Doenças Cardiovasculares , Doença Pulmonar Obstrutiva Crônica , Apneia Obstrutiva do Sono , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Transversais , Vasodilatação , Artéria Braquial , Projetos Piloto , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/complicações , Síndrome , Acelerometria , Exercício FísicoRESUMO
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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Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Qualidade de Vida , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/complicações , Ácido Micofenólico/uso terapêutico , Imunossupressores/uso terapêutico , Ciclofosfamida/uso terapêutico , Pulmão , Progressão da DoençaRESUMO
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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Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Estudos Retrospectivos , Qualidade de Vida , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/complicações , Dispneia/tratamento farmacológico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológicoRESUMO
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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Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/complicações , Qualidade de Vida , Imunossupressores/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , PulmãoRESUMO
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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Indóis , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Qualidade de Vida , Imunossupressores/uso terapêutico , Progressão da Doença , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicaçõesRESUMO
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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Anticorpos Monoclonais Humanizados , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Estudos Prospectivos , Qualidade de Vida , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Pulmão , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/complicações , Capacidade Vital , Progressão da DoençaRESUMO
PURPOSE: Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity, whereas the underlying mechanism is still eluding, the thought participants are chronic intermittent hypoxia with consequent increase in the reactive oxygen species, leading to endothelial cell damage and dysfunction in these patients. As the hydroxyl radical (·OH) mediates the vascular smooth muscle relaxation, identification of its scavengers might reveal sentinel markers of decreased vascular responsiveness and worse long-term comorbid outcome. We therefore assessed leptin's scavenger effect on (â)OH using the electronic paramagnetic resonance (EPR) method. METHODS: The (â)OH was generated by the Fenton reaction in the presence of spin-trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DMPO) with various concentrations of leptin (0.25, 2.5, and 25 µg/ml) and without leptin. EPR spectrometer settings were: modulation frequency, 100 kHz; X band microwave frequency, 9.5 GHz; microwave power, 20 mW (milliwatts); modulation amplitude, 1.0 G (gauss); time constant, 160 s; scan time, 200 s; and receiver gain, 1 × l0(5). EPR signal intensity between 3,440 and 3,540 G of measurements taken in at least three separate experiments was reported. Mannitol, a known (â)OH scavenger, at 100 mM significantly decreased the DMPO-OH adduct formation and was used as the active-control agent. RESULTS: Leptin added to aqueous solutions at all concentrations was associated with a statistically significant decrease in EPR signal compared with controls due to its scavenging activity towards the ·OH. CONCLUSIONS: Leptin could be further investigated as a sentinel biomarker of decreased vascular responsiveness and future risk of atherosclerotic disease in obese OSA patients.
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Endotélio Vascular/metabolismo , Sequestradores de Radicais Livres/química , Radical Hidroxila/química , Leptina/química , Estresse Oxidativo , Apneia Obstrutiva do Sono/metabolismo , Vasodilatação , Espectroscopia de Ressonância de Spin Eletrônica , Endotélio Vascular/fisiopatologia , Sequestradores de Radicais Livres/metabolismo , Humanos , Radical Hidroxila/metabolismo , Leptina/metabolismo , Manitol/química , Apneia Obstrutiva do Sono/fisiopatologiaRESUMO
INTRODUCTION: As in obstructive sleep apnea (OSA), the chronic cycles of hypoxia and reoxygenation are thought to be conducive of oxidative stress (OS) with generation of reactive oxygen species, identifying effective mechanisms of protection against oxidant-mediated tissue damage becomes of outmost importance. Leptin's role had been recently extended into that of participant to OS; while its exact role in this process is yet to be defined, elevated leptin levels correlate significantly with several indices of OSA disease severity such as nocturnal hypoxemia, possibly acting as a counteractive mechanism against the chronic intermittent hypoxia-related OS and serving as a marker of future risk of atherosclerotic disease. We therefore investigated leptin's antioxidant mechanism on superoxide (O (2) (-â¢) ) anions using spectrophotometry and electron paramagnetic resonance (EPR). METHODS: The O (2) (-â¢) was generated by oxidation of xanthine (XAN) by xanthine oxidase (XO) in the presence of spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide with various concentrations of leptin (0.001, 0.01, 0.1, and 1 mg/ml) and without leptin. Signal intensity between 3,440 and 3,540 G was expressed as standard means ± SD. The activity of leptin on XO was determined by monitoring the conversion of XAN to uric acid at 293 nm using a Beckman DU 800 UV-visible spectrophotometer. RESULTS: Leptin added to aqueous solutions at 0.1 and 1 mg/ml concentrations was associated with a statistically significant decrease in the EPR signal due to leptin's direct scavenging activity towards the O (2) (-â¢) . CONCLUSION: Leptin is an antioxidant agent of possible use as a marker of OS and future risk of atherosclerotic disease in OSA.
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Antioxidantes/fisiologia , Espectroscopia de Ressonância de Spin Eletrônica , Leptina/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Leptina/farmacologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismoRESUMO
Despite the heterogeneity of data on the role of noninvasive ventilation (NIV) in severe stable chronic obstructive pulmonary disease with chronic hypercapnia, the current evidence supports the use of NIV in select populations and phenotypes. The Center for Medicare and Medicaid Services reimbursement criteria are complex, and the practice of navigating the most efficient method to initiate NIV therapy continues to be challenging. These patients optimally require referral to a medical center that has physicians with specific training in pulmonary and sleep medicine, who can navigate the specific needs for the use of NIV.
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Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Idoso , Estados Unidos , Humanos , Hipercapnia/terapia , Medicare , Doença Pulmonar Obstrutiva Crônica/terapiaRESUMO
A new era in guideline creation began in 2011 with publication of the Institute of Medicine (now the National Academy of Medicine) Standards for Developing Trustworthy Clinical Practice Guidelines. The American Thoracic Society (ATS) was committed to developing guidelines in accordance with the new standards and decided that an experienced guideline methodologist would be required on ATS guideline projects to ensure correct implementation of the standards. The ATS Guideline Methodology Training Program was launched to increase the pool of trained methodologists. Each year, accepted trainees (methodology scholars) attend a workshop that introduces them to the terminology and process of guideline development and are given the option of participating in a guideline project. Scholars work with the mentorship of a lead methodologist to conduct and then present a systematic review to the guideline committee, discuss the evidence, and participate in the development of evidence-based graded recommendations. Scholars have participated in 22 ATS guidelines over the past 9 years, and most remain engaged in guideline development. For the past 2 years, the methodological aspects of all ATS guideline projects were led by graduates of the training program, and several scholars have accepted positions to lead guidelines for other professional societies. Guideline methodology is particularly suitable for clinician educators because the work is clinically oriented, and guidelines confer high academic capital. Those who elect not to continue in guideline development still acquire the skills to perform and publish systematic reviews, as well as to educate trainees in reading and reviewing literature.
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Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF. Data Extraction: Mortality, disease progression, lung function, and adverse event data were extracted. Meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group approach was used to assess the quality of evidence. Synthesis: Two studies met inclusion criteria. Meta-analyses revealed that changes in forced vital capacity (FVC) percent predicted (mean difference [MD], 2.3%; 95% confidence interval [CI], 0.5-4.1%), the FVC in milliliters (MD, 100.0 ml; 95% CI, 98.1-101.9 ml), and the 6-minute-walk distance in meters (MD, 25.2 m; 95% CI, 8.3-42.1 m) all favored pirfenidone over placebo. The changes in the diffusing capacity of the lung for carbon monoxide (DLCO) in millimoles per kilopascal per minute (MD, 0.40 mmol/kPa/min; 95%, CI 0.10-0.70 mmol/kPa/min) and risk of DLCO declining more than 15% (relative risk [RR], 0.27; 95% CI, 0.08-0.95) also favored pirfenidone. The risks of gastrointestinal discomfort (RR, 1.83; 95% CI, 1.29-2.60) and photosensitivity (RR, 4.88; 95% CI, 1.09-21.83) were higher with pirfenidone. The quality of the evidence was low or very low according to the Grading of Recommendations, Assessment, Development and Evaluation criteria, depending on the outcome. Conclusions: Pirfenidone use in patients with PPF is associated with a statistically significant decrease in disease progression and with protection of lung function. However, there is very low certainty in the estimated effects because of limitations in the available evidence. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.
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Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Progressão da Doença , Humanos , Fibrose Pulmonar/tratamento farmacológico , Piridonas/uso terapêuticoRESUMO
Background: The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). Objective: To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic nintedanib. Data Sources: A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using nintedanib to treat patients with PPF. Data Extraction: Mortality, disease progression, and adverse event data were extracted, and meta-analyses performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach was used to assess the quality of evidence. Synthesis: Two relevant studies were selected. The annual decline in forced vital capacity was less in the nintedanib arm in the overall study population (mean difference [MD], 107 ml/yr; 95% confidence interval [CI], 65.4 to 148.5 ml/yr) and in the subgroups with usual interstitial pneumonia (UIP) pattern of pulmonary fibrosis (MD, 128.2 ml/yr; 95% CI, 70.8 to 185.6 ml/yr), non-UIP patterns of pulmonary fibrosis (MD, 75.3 ml/yr; 95% CI, 15.5 to 135.0 ml/yr), fibrotic connective tissue disease-related ILD (MD, 106.2 ml/yr; 95% CI, 10.6 to 201.9 ml/yr), fibrotic idiopathic nonspecific interstitial pneumonia (MD, 141.7 ml/yr; 95% CI, 46.0 to 237.4 ml/yr), and fibrotic occupational ILD (MD, 252.8 ml/yr; 95% CI, 79.2 to 426.5 ml/yr), but not fibrotic hypersensitivity pneumonitis (MD, 72.9 ml/yr; 95% CI, -8.9 to 154.7 ml/yr), fibrotic sarcoidosis (MD, -20.5 ml/yr; 95% CI, -337.1 to 296.1 ml/yr), or unclassified fibrotic ILD (MD, 68.5 ml/yr; 95% CI, -31.3 to 168.4 ml/yr) when compared with placebo. Gastrointestinal side effects were common. Quality of evidence for the outcomes ranged from very low to moderate GRADE. Conclusions: Nintedanib use in patients with PPF is associated with a statistically significant decrease in disease progression but increase in gastrointestinal side effects regardless of the radiographic pattern of pulmonary fibrosis. However, limitations in the available evidence lead to low certainty in these effect estimates and make definitive conclusions about the differential effects by subtype of ILD difficult to determine. Primary Source of Funding: Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.
Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Progressão da Doença , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis/efeitos adversos , Doenças Pulmonares Intersticiais/tratamento farmacológicoRESUMO
Background: Usual interstitial pneumonia (UIP) is the histopathologic hallmark of idiopathic pulmonary fibrosis (IPF), the prototypical interstitial lung disease (ILD). Diagnosis of IPF requires that a typical UIP pattern be identified by using high-resolution chest computed tomography or lung sampling. A genomic classifier for UIP has been developed to predict histopathologic UIP by using lung samples obtained through bronchoscopy. Objective: To perform a systematic review to evaluate genomic classifier testing in the detection of histopathologic UIP to inform new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guidelines. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched through June 2020. Data Extraction: Data were extracted from studies that enrolled patients with ILD and reported the use of genomic classifier testing. Synthesis: Data were aggregated across studies via meta-analysis. The quality of the evidence was appraised by using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: Genomic classifier testing had a sensitivity of 68% (95% confidence interval [CI], 55-73%) and a specificity of 92% (95% CI, 81-95%) in predicting the UIP pattern in ILD. Confidence in an IPF diagnosis increased from 43% to 93% in one cohort and from 59% to 89% in another cohort. Agreement levels in categorical IPF and non-IPF diagnoses measured by using a concordance coefficient were 0.75 and 0.64 in the two cohorts. The quality of evidence was moderate for test characteristics and very low for both confidence and agreement. Conclusions: Genomic classifier testing predicts histopathologic UIP in patients with ILD with a specificity of 92% and improves diagnostic confidence; however, sensitivity is only 68%, and testing is not widely available.