Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 238
Filtrar
4.
Artigo em Inglês | MEDLINE | ID: mdl-33285079

RESUMO

RATIONALE: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease (ILD) diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE Study, however diagnostic confidence was frequently lower for TBLC than SLB. This secondary analysis aimed to characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance. METHODS: COLDICE was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. Participants underwent both procedures, with blinded pathologist analysis of specimens, applying international guideline criteria. TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed. RESULTS: 65 patients (66·1±9·3yrs; FVC 84·7±14·2%; DLCO 63·4±13·8%) participated in the COLDICE Study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ 0.61, 95% CI 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), while "patchy fibrosis", "fibroblast foci" and "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (OR 23.4, 95%CI 6.36-86.1, p<0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR 1.8, 95% CI 1.08-3.01, p=0.03). Predictors of discordance included older age, family history and radiologic asymmetry. CONCLUSION: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided other guideline criteria features were present. Diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken.

5.
Ann Am Thorac Soc ; 17(12): 1501-1509, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33258669

RESUMO

This report is based on proceedings from the Exposure Assessment Tools for Hypersensitivity Pneumonitis (HP) Workshop, sponsored by the American Thoracic Society, that took place on May 18, 2019, in Dallas, Texas. The workshop was initiated by members from the Environmental, Occupational, and Population Health and Clinical Problems Assemblies of the American Thoracic Society. Participants included international experts from pulmonary medicine, occupational medicine, radiology, pathology, and exposure science. The meeting objectives were to 1) define currently available tools for exposure assessment in evaluation of HP, 2) describe the evidence base supporting the role for these exposure assessment tools in HP evaluation, 3) identify limitations and barriers to each tool's implementation in clinical practice, 4) determine which exposure assessment tools demonstrate the best performance characteristics and applicability, and 5) identify research needs for improving exposure assessment tools for HP. Specific discussion topics included history-taking and exposure questionnaires, antigen avoidance, environmental assessment, specific inhalational challenge, serum-specific IgG testing, skin testing, lymphocyte proliferation testing, and a multidisciplinary team approach. Priorities for research in this area were identified.

6.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33263028

RESUMO

Background: Fibrotic hypersensitivity pneumonitis (f-HP) can exhibit a progressive course similar to idiopathic pulmonary fibrosis (IPF). The lack of diagnostic guidelines and randomised controlled trials in this population represent a significant unmet need. Objectives: To describe our clinical experience with antifibrotics in patients with f-HP. Material and methods: Retrospective study of 30 patients diagnosed with f-HP upon re-evaluation within a multidisciplinary team discussion of 295 consecutive patients (January 2012 to December 2017) who had been diagnosed initially with IPF at outside facilities and were referred to our centres. Results: Pirfenidone was initially administered to 14 (46.7%) patients and nintedanib to 16 (53.3%) patients. There were 26 (86.7%) males, with mean±sd age 70.2±8.4 years. The annual rate of decline in forced vital capacity (FVC) % predicted over the 3-year treatment period adjusted for baseline FVC % pred measurement was 4.2% (95% CI 1.9-6.6%, p=0.001) and 7.5% (95% CI 3.3-11.7%; p=0.001) in imputation analysis. The annual rate of decline in diffusing capacity of the lung for carbon monoxide (D LCO) % predicted throughout the 3-year treatment period adjusted for baseline D LCO % pred was 5.7% (95% CI 3.1-8.4%, p<0.001) and 5.8% (95% CI 3.4-8.1%, p<0.001) in imputation analysis. The nature of adverse events was related to the type of antifibrotic agent administered. Conclusion: In patients with f-HP receiving antifibrotics there is a statistically significant annual decline in FVC % pred and D LCO % pred over a period of 3 years. Prospective randomised trials exceeding 1 year are warranted to determine the long-term efficacy of antifibrotics.

7.
Curr Neuropharmacol ; 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33380301

RESUMO

Oxidative stress, which results in the damage of diverse biological molecules, is a ubiquitous cellular process implicated in the etiology of many illnesses. The sulfhydryl-containing tripeptide glutathione (GSH), which is synthesized and maintained at high concentrations in all cells, is one of the mechanisms by which cells protect themselves from oxidative stress. N-acetylcysteine (NAC), a synthetic derivative of the endogenous amino acid L-cysteine and a precursor of GSH, has been used for several decades as a mucolytic and as an antidote to acetaminophen (paracetamol) poisoning. As a mucolytic, NAC breaks the disulfide bonds of heavily cross-linked mucins, thereby reducing mucus viscosity. In vitro, NAC has antifibrotic effects on lung fibroblasts. As an antidote to acetaminophen poisoning, NAC restores the hepatic GSH pool depleted in the drug detoxification process. More recently, improved knowledge of the mechanisms by which NAC acts has expanded its clinical applications. In particular, the discovery that NAC can modulate the homeostasis of glutamate has prompted studies of NAC in neuropsychiatric diseases characterized by impaired glutamate homeostasis. This narrative review provides an overview of the most relevant and recent evidence on the clinical application of NAC, with a focus on respiratory diseases, acetaminophen poisoning, disorders of the central nervous system (chronic neuropathic pain, depression, schizophrenia, bipolar disorder, and addiction), cardiovascular disease, contrast-induced nephropathy, and ophthalmology (retinitis pigmentosa).

9.
Arthritis Rheumatol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33142016

RESUMO

OBJECTIVE: In the SENSCIS trial in subjects with systemic sclerosis-associated ILD (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) over 52 weeks by 44% versus placebo. We investigated the effects of nintedanib on categorical changes in FVC and other measures of ILD progression. METHODS: In post-hoc analyses, we assessed the proportions of subjects with categorical changes in FVC % predicted at week 52 and the time to absolute decline in FVC ≥5% predicted or death and absolute decline in FVC ≥10% predicted or death. RESULTS: A total of 288 subjects received nintedanib and 288 received placebo. At week 52, in subjects treated with nintedanib and placebo, respectively, 55.7% and 66.3% had any decline in FVC % predicted, 13.6% and 20.1% had an FVC decline >5%-≤10% predicted, and 3.5% and 5.2% had an FVC decline >10%-≤15% predicted; 34.5% and 43.8% had a decrease in FVC ≥3.3% predicted (proposed minimal clinically important difference [MCID] for worsening of FVC), while 23.0% and 14.9% had an increase in FVC ≥3.0% predicted (proposed MCID for improvement in FVC). Over 52 weeks, the hazard ratio for an absolute decline in FVC ≥5% predicted or death with nintedanib versus placebo was 0.83 (95% CI: 0.66, 1.06) (P=0.14) and the hazard ratio for an absolute decline in FVC ≥10% predicted was 0.64 (95% CI: 0.43, 0.95); P=0.029. CONCLUSION: These results suggest that nintedanib has a clinically relevant benefit on the progression of SSc-ILD.

10.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33020069

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.


Assuntos
Comitês Consultivos/organização & administração , Betacoronavirus , Consenso , Infecções por Coronavirus/epidemiologia , Cooperação Internacional , Pneumonia Viral/epidemiologia , Pneumologia/normas , Sociedades Médicas , Europa (Continente) , Humanos , Pandemias , Estados Unidos
11.
Curr Opin Pulm Med ; 26(5): 487-495, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32740379

RESUMO

PURPOSE OF REVIEW: In this review, the authors discuss systemic sclerosis-associated interstitial lung disease (SSc-ILD) with a focus on recent developments in diagnosis, surveillance, and management. RECENT FINDINGS: With advances in the management of SSc, the importance of ILD has been increasingly recognized and is the leading cause of mortality. Early detection is essential, and a combination of lung function testing and chest imaging are key tools in diagnosis and surveillance. The foundation of treatment is immunomodulation with recent studies identifying several potential new agents. The use of therapies targeting pro-fibrotic pathways have demonstrated significant effects on lung function decline and represent the latest advance in therapy for SSc-ILD. SUMMARY: Recent studies support the use of newer therapies in SSc-ILD including antifibrotic agents. The identification and management of comorbidities is important, and lung transplantation is a viable option for patients with advanced disease.

13.
Am J Epidemiol ; 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32803215

RESUMO

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models but human studies are lacking. We examined associations of circulating levels of DHA, and other polyunsaturated fatty acids, with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA, n=6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000-2012), Framingham Heart Study (2005-2011), and Age Gene/Environment Susceptibility (2002-2006) Study (total n=10,193). Polyunsaturated fatty acid levels were from fasting blood samples and extracted from plasma phospholipids (MESA and Age Gene/Environment Susceptibility) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalizations due to ILD (adjusted rate ratio 0.69 per standard deviation increment (95% CI 0.48, 0.99) and a lower rate of death due to ILD (adjusted hazard ratio 0.68 per standard deviation increment, 95% CI 0.47, 0.98). Higher DHA was associated with less interstitial lung abnormalities on CT (pooled adjusted odds ratio 0.65 per natural log increment; 95% CI 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and less lung abnormalities on CT in a meta-analysis of population-based cohorts.

14.
Ann Am Thorac Soc ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32810411

RESUMO

RATIONALE: Hypersensitivity Pneumonitis (HP) is an interstitial lung disease (ILD) whose diagnosis is based on clinical, radiological, and pathological findings. The evidence supporting transbronchial forceps lung biopsy (TBBx) and transbronchial lung cryobiopsy (TBLC) as sampling techniques to diagnose HP in patients with newly detected ILD has not been reviewed systematically. OBJECTIVE: A systematic review was performed to assess the diagnostic yield and complication rates of TBBx or TBLC in patients with newly detected ILD whose differential diagnosis includes HP and to inform the development of the American Thoracic Society (ATS), Japanese Respiratory Society (JRS), and Asociación Latinoamericana del Tórax (ALAT) clinical practice guideline on the diagnosis of HP. METHODS: Medline, EMBASE and the Cochrane Library were searched through October 2019. Studies that enrolled patients with ILD and reported the diagnostic yield of TBBx or TBLC were selected for inclusion. Data related to diagnostic yield and safety outcomes were extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBBx and TBLC were 37% (95% CI 32-42%) and 82% (95% CI 78-86%) respectively among patients with ILD. Among those diagnosed by TBBx, the proportion with HP could not be determined. However, among those diagnosed by TBLC, 13.4% had HP. TBBx was complicated by moderate to severe bleeding, severe bleeding, and pneumothorax in 4% (95% CI 0-8%), 0% (95% CI 0-1%), and 7% (95% 2-13%) of patients, respectively. TBLC was complicated by any bleeding, severe bleeding, and pneumothorax in 11% (95% CI 7-15%), 0% (95% CI 0-1%), and 11% (95% 9-14%) of patients, respectively. The quality of the evidence was very low due to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. CONCLUSION: Very low quality evidence indicated that TBLC had a higher diagnostic yield than TBBx among patients with ILD, although complications were more common with TBLC.

15.
Ann Am Thorac Soc ; 17(11): 1455-1467, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32757946

RESUMO

Rationale: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) characterized by inflammation and/or fibrosis in response to an inhalational exposure.Objectives: To determine the value of bronchoalveolar lavage (BAL) fluid lymphocyte cellular analysis in the detection of HP among patients with newly detected ILD.Methods: This systematic review was undertaken in the context of development of an American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guideline. The clinical question was, "should patients with newly detected ILD undergo BAL fluid lymphocyte analysis to diagnose HP?" MEDLINE, EMBASE, and the gray literature were searched through October 2019. Studies that reported the percentage of BAL fluid lymphocytes for various ILDs were selected for inclusion. Meta-analyses compared the mean percentage of BAL fluid lymphocytes among patients with HP with that among patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. The sensitivity and specificity by which various percentages of BAL fluid lymphocytes distinguish HP from IPF and sarcoidosis were also evaluated.Results: Eighty-four articles were selected. No randomized trials or observational studies were identified that compared BAL fluid lymphocyte analysis with no BAL fluid lymphocyte analysis in patients with ILD. Included studies were case series describing BAL fluid cell differentials in patients with various ILDs. The percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared with IPF. Similarly, the percentage of BAL fluid lymphocytes was significantly higher in both fibrotic and nonfibrotic HP compared with sarcoidosis. A threshold of 20% BAL fluid lymphocytes distinguished fibrotic HP from IPF with a sensitivity and specificity of 69% and 61%, respectively, and nonfibrotic HP from IPF with a sensitivity and specificity of 95% and 61%, respectively. It distinguished fibrotic HP from sarcoidosis with a sensitivity and specificity of 69% and 26%, respectively, and nonfibrotic HP from sarcoidosis with a sensitivity and specificity of 95% and 26%, respectively.Conclusions: The percentage of BAL fluid lymphocytes is higher in HP than IPF or sarcoidosis. However, a threshold that distinguishes HP from IPF or sarcoidosis with both high sensitivity and high specificity was not identified.

17.
Ann Am Thorac Soc ; 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32780584

RESUMO

RATIONALE: Hypersensitivity Pneumonitis (HP) results from exposure to a variety of stimuli, which are challenging to identify. Questionnaires and serum IgG testing are methods to identify potentially causative exposures. OBJECTIVE: To perform a systematic review to determine the usefulness of questionnaires and serum IgG testing in identifying exposures that may have caused HP. METHODS: This systematic review informed an international, multi-disciplinary panel that developed a clinical practice guideline on the diagnosis of HP for the American Thoracic Society (ATS), Japanese Respiratory Society (JRS), and Asociación Latinoamericana del Tórax (ALAT). MEDLINE, the Cochrane Library, and EMBASE were searched from January 1946 through October 2019 for studies that utilized a questionnaire or serum IgG testing to identify exposures that may have caused HP. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to appraise the quality of the evidence. RESULTS: Searches identified 1,141 and 926 potentially relevant articles for questionnaires and serum IgG testing, respectively. The full texts of 32 and 49 articles, respectively, were reviewed. Two observational studies for questionnaires and 17 observational studies for serum IgG testing were selected. Questionnaires were better at detecting potentially relevant exposures compared to clinical history (100% vs. 26%, RR 3.80, 95% CI 1.79-8.06) and serum IgG testing (100% vs. 63%, RR 1.58, 95% CI 1.12-2.23), but were not different compared to serum IgG plus bronchial challenge testing (59% vs. 65%, RR 0.90, 95% CI 0.65-1.24). Longer, detailed questionnaires were more likely to identify potential exposures. Only 70% of potential exposures identified by questionnaires were subsequently confirmed by environmental testing. Serum IgG testing distinguished HP from healthy exposed and unexposed controls with high sensitivity (90% and 92% respectively) and high specificity (91% and 100% respectively) but did not distinguish HP as effectively from interstitial lung diseases (sensitivity 83% and specificity 68%). CONCLUSION: Using a questionnaire may help clinicians identify potentially relevant exposures when evaluating a patient with newly identified ILD for HP. Serum IgG testing may also identify potentially relevant exposures, but it is poor at distinguishing HP from other types of ILD.

18.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32817115

RESUMO

BACKGROUND: Air pollution is hypothesised to be a risk factor for interstitial lung diseases (ILD). This study systematically reviewed the literature regarding the impact of air pollution on idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (ILD). METHODS: A computer-assisted literature search of electronic databases was performed to identify studies focused on the association between ILDs and air pollution. Other inclusion criteria required that the article had to be: 1) original; 2) a prospective or retrospective study; and 3) fully published in English. Both randomised clinical trials and observational studies were considered. RESULTS: Only seven studies met the inclusion criteria. All studies investigated the relationship between pollution and IPF, except one that dealt with the relationship between pollution and hypersensitivity pneumonitis. Outcome measures included exacerbation of IPF, mortality, disease severity, prevalence of hypersensitivity pneumonitis, progression and incidence of IPF. On the whole, air pollution levels were negatively associated with outcomes in patients with IPF and fibrotic ILD outcome. The heterogeneity in the measurement and reporting of the end-points limited the performance of a quantitative synthesis of data. CONCLUSIONS: This systematic review provides supporting evidence linking exposure to air pollution to poor outcomes in patients with IPF and fibrotic ILD.

19.
Ann Am Thorac Soc ; 17(12): 1620-1628, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32776789

RESUMO

Detailed understanding of longitudinal behavior, response to therapy, and applicable biomarkers for interstitial lung diseases (ILDs) is lacking. There is a need for a large multicenter registry that provides researchers and clinicians access to well-characterized data not limited to patients with idiopathic pulmonary fibrosis. The Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) is a database that collects baseline and longitudinal demographic and clinical information about patients with ILDs in the United States. The objective of this study is to describe the patient population, data collection process, and opportunities for retrospective and prospective research with the PFF-PR. Individuals 18 years or older who had ILD diagnosed and who were seen at PFF-PR centers who provided informed consent were eligible to participate. Baseline and longitudinal demographic, spirometric, radiographic, morbidity, and mortality data are recorded into a secure electronic data capture system. Starting in 2016, the PFF-PR has collected data on 2,003 patients at 42 clinical sites in the United States. At the time of enrollment, the mean age of participants was 68 years old. Most (62%) of participants were male, and 58% had a positive smoking history. The mean forced vital capacity was 69% predicted, and the mean diffusing capacity of the lung for carbon monoxide was 43% predicted. Forty-one percent of patients were using supplemental oxygen, and 39% were on antifibrotic therapy. Reasons for attrition were mostly death or transplant, with low rates of loss to follow-up or withdrawal. The PFF-PR is a large multicenter United States-based registry that provides researchers and clinicians access to well-characterized ILD patient data.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32721166

RESUMO

Rationale Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy (SLB) for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A 'molecular diagnosis of UIP' in transbronchial lung biopsy (TBBx), the Envisia Genomic Classifier, accurately predicted histopathologic UIP. Objectives We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern. Methods Ninety-six patients who had diagnostic lung pathology, as well as a TBBx for molecular testing with Envisia Genomic Classier, were included in this analysis. The classifier results were scored against reference pathology. UIP identified on HRCT as documented by features in local radiologists' reports was compared to histopathology. Measurements and Main Results In 96 patients, the Envisia classifier achieved a specificity of 92.1% [CI:78.6%-98.3%] and a sensitivity of 60.3% [CI:46.6%-73.0%] for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology with a sensitivity of 34.0% [CI:21.5%-48.3%], and a specificity of 96.9% [CI:83.8 - 100]). In conjunction with HRCT patterns of UIP, the Envisia classifier results identified 24 additional UIP patients (sensitivity 79.2% specificity 90.6%). Conclusions In 96 patients with suspected ILD, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an ILD (especially IPF) diagnosis without the need for SLB.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA