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1.
J Immunol ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213567

RESUMO

The chemokine CXCL13 controls the normal organization of secondary lymphoid tissues and the neogenesis of ectopic lymphoid structures in nonlymphoid organs, particularly the lungs. The progression and severity of idiopathic pulmonary fibrosis (IPF), a fatal and irreversible interstitial lung disease, is predicted by the circulating blood concentrations of CXCL13. Although CXCL13 is produced by pulmonary tissues, it has not been determined which cells are involved. This study examines CXCL13 production by lung tissue macrophages from patients with IPF and the signaling pathways controlling CXCL13 gene expression in human alveolar macrophages (AM) and monocyte-derived macrophages (MoDM). CXCL13 is found in CD68- and CD206-positive AM from patients with IPF, and the CXCL13 gene is induced in these macrophages and MoDM when they are stimulated with LPS. We found that TNF-α and IL-10 control optimal CXCL13 gene expression in MoDM and possibly in AM by activating the NF-κB and JAK/STAT pathways, respectively. We also found that blood TNF-α and CXCL13 concentrations are significantly correlated in patients with IPF, suggesting that TNF-α contributes to CXCL13 production in humans. In conclusion, the results of this study demonstrate that AM from patients with IPF produces CXCL13 and that the NF-κB and JAK/STAT pathways are required to induce the expression of this major chemokine.

2.
Front Immunol ; 11: 219, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133004

RESUMO

Inhalation of crystalline silica (SiO2) is a risk factor of systemic autoimmune diseases such as systemic sclerosis (SSc) and fibrotic pulmonary disorders such as silicosis. A defect of apoptotic cell clearance (i.e., efferocytosis, a key process in the resolution of inflammation) is reported in macrophages from patients with fibrotic or autoimmune diseases. However, the precise links between SiO2 exposure and efferocytosis impairment remain to be determined. Answering to this question may help to better link innate immunity and fibrosis. In this study, we first aim to determine whether SiO2 might alter efferocytosis capacities of human and mouse macrophages. We secondly explore possible mechanisms explaining efferocytosis impairment, with a specific focus on macrophage polarization and on the RhoA/ROCK pathway, a key regulator of cytoskeleton remodeling and phagocytosis. Human monocyte-derived macrophages (MDM) and C57BL/6J mice exposed to SiO2 and to CFSE-positive apoptotic Jurkat cells were analyzed by flow cytometry to determine their efferocytosis index (EI). The effects of ROCK inhibitors (Y27632 and Fasudil) on EI of SiO2-exposed MDM and MDM from SSc patients were evaluated in vitro. Our results demonstrated that SiO2 significantly decreased EI of human MDM in vitro and mouse alveolar macrophages in vivo. In human MDM, this SiO2-associated impairment of efferocytosis, required the expression of the membrane receptor SR-B1 and was associated with a decreased expression of M2 polarization markers (CD206, CD204, and CD163). F-actin staining, RhoA activation and impairment of efferocytosis, all induced by SiO2, were reversed by ROCK inhibitors. Moreover, the EI of MDM from SSc patients was similar to the EI of in vitro- SiO2-exposed MDM and Y27632 significantly increased SSc MDM efferocytosis capacities, suggesting a likewise activation of the RhoA/ROCK pathway in SSc. Altogether, our results demonstrate that SiO2 exposure may contribute to the impairment of efferocytosis capacities of mouse and human macrophages but also of MDM in SiO2-associated autoimmune diseases and fibrotic disorders such as SSc; in this context, the silica/RhoA/ROCK pathway may constitute a relevant therapeutic target.

3.
Infection ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32056143

RESUMO

PURPOSE: To describe the burden, and characteristics, of influenza-like illness (ILI) associated with non-influenza respiratory viruses (NIRV). METHODS: We performed a prospective, multicenter, observational study of adults admitted with ILI during three influenza seasons (2012-2015). Patients were screened for picornavirus, respiratory syncytial virus (RSV), coronavirus, human metapneumovirus, adenovirus, bocavirus, parainfluenza virus, and influenza, by PCR on nasopharyngeal samples. We excluded patients coinfected with NIRV and influenza. RESULTS: Among 1421 patients enrolled, influenza virus was detected in 535 (38%), and NIRV in 215 (15%), mostly picornavirus (n = 61), RSV (n = 53), coronavirus 229E (n = 48), and human metapneumovirus (n = 40). In-hospital mortality was 5% (NIRV), 4% (influenza), and 5% (no respiratory virus). As compared to influenza, NIRV were associated with age (median, 73 years vs. 68, P = 0.026), chronic respiratory diseases (53% vs. 45%, P = 0.034), cancer (14% vs. 9%, P = 0.029), and immunosuppressive drugs (21% vs. 14%, P = 0.028), and inversely associated with diabetes (18% vs. 25%, P = 0.038). On multivariable analysis, only chronic respiratory diseases (OR 1.5 [1.1-2.0], P = 0.008), and diabetes (OR 0.5 [0.4-0.8], P = 0.01) were associated with NIRV detection. CONCLUSIONS: NIRV are common in adults admitted with ILI during influenza seasons. Outcomes are similar in patients with NIRV, influenza, or no respiratory virus.

4.
BMC Pulm Med ; 20(1): 3, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914963

RESUMO

BACKGROUND: The two 52-week INPULSIS trials investigated nintedanib versus placebo in patients with IPF, FVC ≥50% predicted and DLco 30-79% predicted. The 24-week INSTAGE trial investigated nintedanib plus sildenafil versus nintedanib alone in patients with IPF and DLco ≤35% predicted. We used data from INPULSIS and INSTAGE to compare the effects of nintedanib in patients with IPF with less versus more severe impairment in gas exchange at baseline. METHODS: Analyses were conducted in patients treated with nintedanib alone in the INPULSIS and INSTAGE trials and in patients treated with placebo in the INPULSIS trials. Outcomes included the rate of decline in FVC over 24 weeks, the proportions of patients who had a confirmed or suspected idiopathic acute exacerbation over 24 weeks, deaths over 24 weeks, and adverse events. Analyses were descriptive. RESULTS: In total, 638 and 136 patients received nintedanib alone in the INPULSIS and INSTAGE trials, respectively, and 423 patients received placebo in the INPULSIS trials. Rates of FVC decline were - 52.3 and - 66.7 mL/24 weeks in patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and - 102.8 mL/24 weeks in patients treated with placebo in INPULSIS. Confirmed or suspected idiopathic acute exacerbations were reported in 0.6 and 3.7% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 2.1% of patients treated with placebo in INPULSIS. Deaths occurred in 2.0, 11.0 and 1.9% of patients in these groups, respectively. Diarrhoea adverse events were reported in 52.5 and 48.5% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 16.1% of patients treated with placebo in INPULSIS. CONCLUSIONS: Based on data from the INSTAGE and INPULSIS trials, nintedanib had a similar effect on FVC decline over 24 weeks, and a similar safety and tolerability profile, in patients with IPF and more versus less severe impairment in gas exchange. These data support the use of nintedanib in patients with IPF who have advanced disease. TRIAL REGISTRATION: INPULSIS (NCT01335464 and NCT01335477); INSTAGE (NCT02802345).

5.
J Autoimmun ; 106: 102338, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31570253

RESUMO

BACKGROUND: Progressive fibrosing interstitial lung disease (ILD) is rarely associated with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). This study focused on the outcomes of ILD patients with associated AAV (AAV-ILD). METHODS: AAV-ILD (cases: microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) with ILD) were compared to AAV patients without ILD (controls). ILD was defined as a usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP) pattern. Two controls were matched to each case for age (>or ≤65 years), ANCA status (PR3-or MPO-positive) and creatininemia (≥or <150 µmol/L). RESULTS: Sixty-two cases (89% MPO-ANCA+) were included. Median age at AAV diagnosis was 66 years. ILD (63% UIP), was diagnosed before (52%) or simultaneously (39%) with AAV. Cases versus 124 controls less frequently had systemic vasculitis symptoms. One-, 3- and 5-year overall survival rates, respectively, were: 96.7%, 80% and 66% for cases versus 93.5%, 89.6% and 83.8% for controls (p = 0.008). Multivariate analyses retained age >65 years (hazard ratio (HR) 4.54; p < 0.001), alveolar haemorrhage (HR 2.25; p = 0.019) and UIP (HR 2.73; p = 0.002), but not immunosuppressant use, as factors independently associated with shorter survival. CONCLUSION: For AAV-ILD patients, only UIP was associated with poorer prognosis. Immunosuppressants did not improve the AAV-ILD prognosis. But in analogy to idiopathic pulmonary fibrosis, anti-fibrosing agents might be useful and should be assessed in AAV-ILD patients with a UIP pattern.

6.
COPD ; 17(1): 7-14, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31854207

RESUMO

Our main objective was to demonstrate that, in smoker patients hospitalised for Chronic Obstructive Pulmonary Disease (COPD) exacerbation, early initiation of varenicline during 12 weeks, combined with an intensive counselling, is associated with a higher continuous abstainers rate (CAR) at one year as compared to intensive counselling alone. In this multicenter, prospective, double-blind, randomised study, 81 smoking COPD patients hospitalised for an acute exacerbation for at least 24 h were allocated to receive either varenicline (n = 42) or placebo (n = 39) for 12 weeks, in association with an intensive counselling in the 2 groups, and followed up for 40 weeks. The primary outcome was CAR at week 52. Secondary outcomes included CAR at week 12 and 26, partial abstinence rate (PAR) at week 12, 26 and 52, nicotinic substitute consumption and adverse events. At week 52, CAR was not different in placebo and varenicline groups (25.6%). At week 12, CAR was significantly higher in the varenicline group (50%) as compared to placebo group (27%) (p = 0.041). Nicotine consumption was significantly higher at week 52 in the placebo group (55.3%) as compared to the varenicline group (24.4%) (p = 0.005). There was no significant difference in PAR at week 12, 26 and 52; the frequency of adverse events was similar between the two groups. Among active smoker COPD patients with exacerbation, 12-week varenicline associated with intensive counselling for smoking cessation increased the rate of continuous abstainers as compared to placebo. However, benefit was not maintained after varenicline discontinuation.Clinical Trials Registration: URL: http://www.controlled-trials.com. Unique identifier: NCT01694732.

8.
Respir Res ; 20(1): 124, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208466

RESUMO

Allergic mechanisms related to environmental and occupational exposure have been suggested to contribute to the development of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To investigate the relationships between atopy markers, persistent airflow limitation (PAL) and occupational exposure in dairy farmers. METHODS: Clinical and biological (total IgE and 21 allergen specific IgE) markers of atopy were assessed in 101 dairy farmers with PAL (DF-PAL), 85 non-farmers with PAL (NF-PAL) (both groups were prospectively included from a screening program performed between 2011 and 2015), and matched controls, i.e. 98 farmers without PAL (DF-controls) and 89 non-farming subjects without PAL (NF-controls). Occupational exposure in farmers was estimated using a validated questionnaire. RESULTS: Prevalence of allergy history was significantly higher in DF-PAL and in NF-PAL than in controls. Polysensitization, and sensitization to seasonal and food allergens were more frequent in DF-PAL than in DF-controls, respectively: 13.8% vs 1% (adjusted odds ratio (aOR): 17.5 (2.2-134), 11.9% vs 3.1% (aOR: 4.4 (1.2-7.2) and 16.8% vs 4.1% (aOR: 5.2 (1.7-7.2)). The prevalence of atopy markers was similar between NF-PAL patients and NF-controls. CONCLUSIONS: PAL in farmers is associated with a high rate of markers of atopy, supporting atopy as a risk indicator. Clinical trial registered with ClinicalTrials.gov (NCT02540408).


Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Indústria de Laticínios , Fazendeiros , Exposição Ocupacional/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Doenças dos Trabalhadores Agrícolas/diagnóstico , Doenças dos Trabalhadores Agrícolas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/imunologia , Fatores de Risco
12.
Int Immunopharmacol ; 72: 112-123, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30974282

RESUMO

The tyrosine kinase inhibitor, Nintedanib (NTD), has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). In cell-free systems, NTD was recently shown to inhibit kinase activity of the human recombinant colony-stimulating factor 1 (CSF1) receptor (CSF1R) which mediates major functions of pulmonary macrophages. In the present study, we have investigated the effects of NTD on the phenotype of human monocyte-derived macrophages controlled by CSF1 in order to identify its anti-inflammatory properties via CSF1R inhibition. NTD (0.01 to 1 µM) prevented the CSF1-induced phosphorylation of CSF1R and activation of the downstream signaling pathways. NTD, like the CSF1R inhibitor GW2580, significantly decreased the adhesion of macrophages and production of the chemokine ligand (CCL) 2. NTD also altered the polarization of macrophages to classical M1 and alternative M2a macrophages. It reduced the secretion of several pro-inflammatory and/or pro-fibrotic cytokines (IL-1ß, IL-8, IL-10 and CXCL13) by M1 macrophages but did not prevent the expression of M1 markers. While NTD (50-200 nM) partially blocked the synthesis of M2a markers (CD11b, CD200R, CD206, and CD209), it did not reduce synthesis of the M2a pro-fibrotic cytokines CCL22 and PDGF-BB, and increased CCL18 release when used at its highest concentration (1 µM). The effects of NTD on macrophage polarization only was partially mimicked by GW2580, suggesting that the drug inhibits other molecules in addition to CSF1R. In conclusion, NTD alters the CSF1-controlled phenotype of human macrophages mainly by blocking the activation of CSF1R that thus constitutes a new molecular target of NTD, at least in vitro.


Assuntos
Indóis/farmacologia , Macrófagos/efeitos dos fármacos , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Células Cultivadas , Citocinas/metabolismo , Humanos , Fibrose Pulmonar Idiopática , Macrófagos/metabolismo , Fenótipo
13.
Respiration ; 98(1): 19-28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30965332

RESUMO

BACKGROUND: The European observational, prospective PASSPORT study evaluated the long-term safety of pirfenidone under real-world conditions in idiopathic pulmonary fibrosis (IPF), over up to 2 years following its initiation. OBJECTIVES: The FAS (French Ancillary Study) assessed the clinical outcomes of IPF patients participating in PASSPORT (n = 192). METHODS: Efficacy data were collected retrospectively and prospectively. The primary efficacy endpoints were: change in percent predicted forced vital capacity (FVC) and change in the distance travelled during the 6-min walk test (6MWD). RESULTS: The mean baseline FVC was 71.7% of predicted value. The mean absolute change in the percentage of predicted FVC was -2.4% and -3.8% at months 12 and 24. The mean change in 6MWD was 8.6 and 3.1 m at months 12 and 24, with a range of 23.4-51.7 m. Acute IPF exacerbation and pulmonary hypertension occurred in 20.0 and 8.4% of patients, respectively. The most common reasons for prematurely discontinuing PASSPORT were adverse drug reactions (ADRs) related to pirfenidone (31.3%), death (11.5%), and disease progression (10.9%). The median progression-free survival was 18.4 months (95% CI 12.9, not estimable). The median exposure was 16.3 months (0.5-28.5). The most frequently reported ADRs leading to pirfenidone discontinuation were decreased weight (4.2%), rash (4.2%), and photosensitivity reactions (3.1%). CONCLUSIONS: The efficacy data of FAS are consistent with the efficacy results of published phase III clinical trials in IPF. Approximately one third of IPF patients treated with pirfenidone in real-life settings were still under treatment 2 years after initiation. Safety data are consistent with the known safety profile of pirfenidone.

14.
Nutrition ; 62: 115-121, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30878815

RESUMO

OBJECTIVES: Little is known about the indicators to assess malnutrition in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to determine the following: 1) the prevalence of malnutrition in IPF patients; 2) the nutritional indicators predictive of low fat-free mass (FFM) as measured by bioimpedance analysis; 3) the IPF patients' characteristics associated with low FFM. METHODS: The IPF patients were consecutively recruited in a referral center for rare pulmonary diseases. Malnutrition was defined as a fat-free mass index (FFMI) = FFM (kg) / (height [m]2) <17 (men) or <15 (women). Nutritional assessment included body mass index (BMI), mid-arm circumference (MAC), triceps skinfold thickness, analogue food intake scale, and serum albumin and transthyretin. The primary endpoint was FFMI. Area under the receiver operating characteristic curve (AUC) assessed low FFMI prediction from nutritional indicators. Multivariable logistic regression determined variables associated with low FFMI. RESULTS: Eighty-one patients were consecutively recruited. Low FFMI prevalence was 28% (23 of 81). BMI AUC was 0.91 (95% confidence interval [CI], 0.84‒0.97) and MAC AUC was 0.85 (0.76‒0.94). Multivariable analysis associated BMI (odds ratio [OR] 0.26 [95% CI, 0.12-0.54], P = 0.0003), male sex (OR 0.02 [0.00-0.33], P = 0.005), and smoking (OR 0.10 [0.01-0.75], P = 0.024) with a lower risk of malnutrition. CONCLUSIONS: Malnutrition occurred in nearly one-third of IPF patients. Malnutrition screening should become systematic based on BMI and MAC, which are good clinical indicators of low FFMI. We propose a practical approach to screen malnutrition in IPF patients.

15.
Eur Respir Rev ; 28(151)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30814138

RESUMO

The increasingly female face of chronic obstructive pulmonary disease (COPD) prevalence among women has equalled that of men since 2008, due in part to increased tobacco use among women worldwide and exposure to biomass fuels. This finding is supported by a number of characteristics. There is evidence of susceptibility to smoking and other airborne contaminants, along with epidemiological and phenotypic manifestations. COPD has thus become the leading cause of death in women in the USA. The clinical presentation is characterised by increasingly pronounced dyspnoea with a marked tendency towards anxiety and depression, undernutrition, nonsmall cell lung cancer (especially adenocarcinoma) and osteoporosis. Quality of life is also more significantly impacted. The theories advanced to explain these differences involve the role played by oestrogens, impaired gas exchange in the lungs and smoking habits. While these differences require appropriate therapeutic responses (smoking cessation, pulmonary rehabilitation, long-term oxygen therapy), barriers to the treatment of women with COPD include greater under-diagnosis than in men, fewer spirometry tests and medical consultations. Faced with this serious public health problem, we need to update and adapt our knowledge to the epidemiological changes.


Assuntos
Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologia , Adulto Jovem
18.
Immunol Cell Biol ; 97(3): 340-347, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30426551

RESUMO

A defect in the apoptotic cell clearance (efferocytosis) by phagocytic cells may participate in autoimmunity and chronic inflammation. The mechanisms leading to the emergence of autoimmunity in systemic sclerosis (SSc) are still to be determined. In this study, the efferocytosis capacities of blood monocyte-derived macrophages (MDM) from patients with SSc were evaluated. Blood monocytes obtained from patients with SSc and healthy donors (HD) were differentiated in vitro into macrophages. The capacities of MDM to engulf CFSE+ apoptotic Jurkat human T lymphocytes were compared between SSc MDM and HD using flow cytometry. The expression of classical engulfing receptors in SSc MDM and HD MDM was also evaluated and their involvement in the modulation of efferocytosis was confirmed using a siRNA approach. The mean phagocytic index (PI) reflecting efferocytosis capacities of SSc MDM (PI = 19.3 ± 3.0; n = 21) was significantly decreased in comparison with the PI of HD MDM (PI = 35.9 ± 3.0; n = 31; P < 0.001). In comparison with HD, SSc MDM exhibited a downregulated expression of scavenger receptor (SR)-B1, SR-A1 and integrin ß5 (ITGß5). In HD MDM, the extinction of these receptors was followed by a reduction of efferocytosis only for the repression of ITGß5, suggesting a possible selective role of this integrin in the impaired efferocytosis observed in SSc. As efferocytosis may be at the crossroads of inflammation, autoimmunity and fibrosis, in showing impaired efferocytosis capacities of blood MDM in SSc, our study offers new pathogenesis considerations for the involvement of macrophages in the autoimmune processes driving this disorder.


Assuntos
Macrófagos/imunologia , Fagocitose/imunologia , Escleroderma Sistêmico/imunologia , Estudos de Casos e Controles , Humanos , Cadeias beta de Integrinas/metabolismo , Macrófagos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Receptores Depuradores Classe B/metabolismo , Fatores de Processamento de Serina-Arginina/metabolismo
19.
Environ Res ; 169: 1-6, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30399467

RESUMO

BACKGROUND: The AIRBAg study was designed to assess the prevalence of chronic obstructive pulmonary disease (COPD) in dairy farmers and to define its associated risk factors. METHODS: Between March 2012 and February 2017 randomly selected dairy farmers in the French region of Brittany were asked to complete a self-administered questionnaire and undergo an occupational health check-up with electronic mini-spirometry and standard spirometry. Those having one or more of the following features: chronic cough, chronic bronchitis, wheezing, dyspnea and/or a ratio FEV1/FEV6 < 80% were then referred to a pulmonologist for further check-up including spirometry with a reversibility test. Each COPD case was matched with three controls (dairy farmers and non-farm employees), for sex and age ( ±â€¯5 years). Conditional multivariate logistic regression models were used to estimate the odds ratios between COPD occurrence and various risk factors. RESULTS: The 1203 farmers examined included 525 (43.6%) who were "at risk of bronchial obstruction" and 432 (35.9%) of these saw the pulmonologist. This screening identified 16 (1.3%) cases of COPD, including eight non-smokers and five with an FEV1 < 80% of predicted values. Their average age was 54.6 ( ±â€¯7.7) years and 10 of them were men. None complained of illness before the study. Multivariate analyses revealed no significant occupational risk factors for COPD. CONCLUSIONS: This unexpected result may be because Breton dairy farms began to modernize early (1950s), giving rise to conditions with much lower exposure to airborne contaminants.


Assuntos
Indústria de Laticínios/estatística & dados numéricos , Fazendeiros/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Espirometria
20.
Eur Respir Rev ; 27(150)2018 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-30578333

RESUMO

A proportion of patients with interstitial lung diseases (ILDs) are at risk of developing a progressive-fibrosing phenotype, which is associated with a deterioration in lung function and early mortality. In addition to idiopathic pulmonary fibrosis (IPF), fibrosing ILDs that may present a progressive phenotype include idiopathic nonspecific interstitial pneumonia, connective tissue disease-associated ILDs, hypersensitivity pneumonitis, unclassifiable idiopathic interstitial pneumonia, ILDs related to other occupational exposures and sarcoidosis. Corticosteroids and/or immunosuppressive therapies are sometimes prescribed to patients with these diseases. However, this treatment regimen may not be effective, adequate on its own or well tolerated, suggesting that there is a pressing need for efficacious and better tolerated therapies. Currently, the only approved treatments to slow disease progression in patients with IPF are nintedanib and pirfenidone. Similarities in pathobiological mechanisms leading to fibrosis between IPF and other ILDs that may present a progressive-fibrosing phenotype provide a rationale to suggest that nintedanib and pirfenidone may be therapeutic options for patients with the latter diseases.This review provides an overview of the therapeutic options currently available for patients with fibrosing ILDs, including fibrosing ILDs that may present a progressive phenotype, and explores the status of the randomised controlled trials that are underway to determine the efficacy and safety of nintedanib and pirfenidone.


Assuntos
Indóis/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/tratamento farmacológico , Piridonas/uso terapêutico , Progressão da Doença , Humanos , Indóis/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Fenótipo , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/fisiopatologia , Piridonas/efeitos adversos , Fatores de Risco , Resultado do Tratamento
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