RESUMO
INTRODUCTION: One of the major concerns with post-acute sequelae of COVID-19 (PASC) is the development of pulmonary fibrosis, for which no approved pharmacological treatment exists. Therefore, the primary aim of this open-label study was to evaluate the safety and the potential clinical efficacy of a prolonged-release pirfenidone formulation (PR-PFD) in patients having PASC-pulmonary fibrosis. METHODS: Patients with PASC-pulmonary fibrosis received PR-PFD 1800 mg/day (1200 mg in the morning after breakfast and 600 mg in the evening after dinner) for three months. Blood samples were taken to confirm the pharmacokinetics of PR-PFD, and adverse events (AEs) were evaluated monthly using a short questionnaire. Symptoms, dyspnea, and pulmonary function tests (spirometry, diffusing capacity for carbon monoxide, plethysmography, and 6-min walk test [6MWT]) were evaluated at baseline, and one and three months after having started the PR-PFD treatment. RESULTS: Seventy subjects with mild to moderate lung restriction were included. The most common AEs were diarrhea (23%), heartburn (23%), and headache (16%), for which no modifications in the drug study were needed. Two patients died within the first 30 days of enrolment, and three opted not to continue the study, events which were not associate with PR-PFD. Pulmonary function testing, 6MWT, dyspnea, symptoms, and CT scan significantly improved after three months of treatment with PR-PFD. CONCLUSION: In patients with PASC pulmonary fibrosis, three months' treatment with PR-PFD was safe and showed therapeutic efficacy. Still, it remains to be seen whether the pulmonary fibrotic process remains stable, becomes progressive or will improve.
Assuntos
COVID-19 , Fibrose Pulmonar Idiopática , Pneumonia , Humanos , COVID-19/complicações , Progressão da Doença , Dispneia/tratamento farmacológico , Dispneia/etiologia , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/diagnóstico , Fenótipo , Pneumonia/tratamento farmacológico , Piridonas/efeitos adversosRESUMO
Genotoxicity caused by tobacco smoke was assessed in peripheral blood lymphocytes of smokers living in Mexico City by determining sister chromatid exchange (SCE), cell proliferation kinetics (CPK), replication index (RI) and mitotic index (MI). Nicotine levels, and its major metabolite cotinine, were also estimated in urine samples using gas-chromatography-mass spectrometry to quantify smoking intensity. The outcome of the analysis and the comparison of the 77-smoker group with a non-smoking control group showed that moderate and heavy smokers exhibited significant differences (P < 0.001 and P < 0.05, respectively) in CPK, with an underlying delay in the cellular cycle; similarly, RI was significantly different in these groups (P < 0.001 and P < 0.0001, respectively). There were significant correlations (P < 0.05) between age and number of years the subject had been smoking, as well as between RI and nicotine and cotinine levels and between CPK (M1, M2 and M3) and nicotine and cotinine levels. Smokers were classified for the analysis according to the nicotine levels (it is in relation to number of cigarettes smoked per day) found in urine (ng/mL) as: light (10-250), moderate (251-850) and heavy (851-4110). Significant differences in CPK were found (P < 0.05) between moderate and heavy smokers and non-smokers. Significant differences in RI were found between moderate (P < 0.001) and heavy smokers (P < 0.0001) and non-smokers, but not for the light smoking group. MI was determined in 57 of the smokers, whereas SCE frequency was only recorded in 34 smokers. Both parameters yielded no significant differences, nor correlations with any of the assessed variables. In conclusion, cytokinetic and cytostatic effects were mainly detected in heavy and moderate smokers. Cell cycle delay and RI decrease were found in all ;healthy' smokers. The nicotine and cotinine exposure (causing oxidative damage to DNA) may have implications in the decrease in cell replication due to direct damage to DNA and/or a decrease in the DNA repair mechanisms. Alternatively, nicotine and cotinine may possibly induce apoptosis.
Assuntos
Proliferação de Células/efeitos dos fármacos , Cotinina/toxicidade , Linfócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Troca de Cromátide Irmã/efeitos dos fármacos , Fumar/efeitos adversos , Adulto , Estudos de Casos e Controles , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Cotinina/urina , Dano ao DNA , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Cinética , Linfócitos/patologia , Masculino , México , Pessoa de Meia-Idade , Índice Mitótico , Nicotina/urina , Agonistas Nicotínicos/urina , Estresse Oxidativo/efeitos dos fármacos , Fumar/urinaRESUMO
OBJECTIVES: To determine prevalence, addiction knowledge and attitude on tobacco smoking in a group of smoking physicians (MF) and to compare these variables with smoking non-physicians (FNM) and non-smoking physicians (MNF) from the National Institutes of Health in Mexico (Insalud). MATERIAL AND METHODS: The results of a questionnaire among the three groups were compared. RESULTS: The prevalence of MF (22%) was significantly lower than in FNM (28%), (OR = 0.72, CI = 0.61-0.85). No significant differences regarding addiction and attitudes were found between them. The MNF had better knowledge and attitudes and agreed that their Institute should be a non-smoking area. CONCLUSION: Prevalence of smoking is lower among physicians than among FNM and the similarities between them suggest that addiction can provoke them and that a program for tobacco control is required.
Assuntos
Médicos/estatística & dados numéricos , Fumar/epidemiologia , Adulto , Conhecimentos, Atitudes e Prática em Saúde , Humanos , México , Ocupações , Prevalência , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To determine the prevalence of cigarette smoking at the National Institutes of Health in Mexico (NIHM). MATERIAL AND METHODS: A survey was performed among workers who voluntarily answered a questionnaire. Smokers were identified with two specific questions, and type of employment was classified as physicians, administrative staff, investigators and support personnel. RESULTS: Total prevalence smoking was 28% (of 4,422 answered questionnaires). It was significantly higher among females, among administrative staff, and common-law and separated workers. It was significantly higher at the Mexican Institute of Psychiatry than at the remaining Institutes, even after adjusting for confounding. The prevalence was also higher among physicians from the same Institute. Of the smokers, 46% do so in their work areas and 78% of them would like to quit. CONCLUSIONS: The prevalence of smokers at the NIHM is as high as in the general population and a broad educational program for tobacco control and prevention is needed.
Assuntos
Órgãos Governamentais/estatística & dados numéricos , Fumar/epidemiologia , Pessoal Administrativo/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , México/epidemiologia , Prevalência , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To evaluate the relationship between alveolar macrophage (AM) elastase and plasminogen activator (PA) activities (considered to be potential pathogenetic factors in emphysema) and the development of emphysema in smokers. PARTICIPANTS: Thirty-four healthy smokers >35 years of age (mean+/-SD, 46+/-7 years), with a mean+/-SD of 33+/-10 pack-years of smoking, who were recruited as volunteers. METHODS: Subjects had lung function testing and BAL to obtain AMs; limited high-resolution CT scans of the chest were obtained in 32 subjects to assess the presence of emphysema. Macrophage PA and elastase were determined using AM cultured on (131)I-fibrin-coated plates and 3H-elastin-coated plates, respectively. RESULTS: The number of AMs recovered per milliliter of BAL was significantly greater in the 16 subjects with CT evidence of mild emphysema than the 16 subjects without evidence of emphysema (669+/-301 x 10(3)/mL vs 414+/-268x 10(3)/mL; p=0.01). There was no significant difference between AM elastase or PA activities in the 16 subjects with CT evidence of mild emphysema, when compared with the 16 subjects who had no CT evidence of emphysema (elastase, 2.72+/-1.35 microg vs 2.49+/-0.91 microg elastin per 10(6) AMs per first 24 h; PA, 0.375+/-0.126 vs 0.344+/-0.096 urokinase units/10(6) AMs). There was no significant correlation between levels of PA or elastase activities and FEV1, FEV1/FVC, forced expiratory flow rate between 25% and 75% of the FVC; PA activity but not elastase activity had a significant negative correlation (r=-0.47, p<0.01) with diffusion of carbon monoxide (DCO). The macrophage count in BAL had a significant negative correlation with DCO percent predicted (r=-0.61, p<0.001). CONCLUSIONS: The findings suggest that the number of AMs recovered per milliliter of BAL (presumably indicating the number in the alveolar spaces) is related to the development of emphysema in smokers as indicated by CT scan of the chest and DCO. The results also suggest that the level of PA enzyme activity in AMs may be a pathogenetic factor in the decrease in DCO in smokers.
Assuntos
Pulmão/diagnóstico por imagem , Macrófagos Alveolares/enzimologia , Elastase Pancreática/metabolismo , Ativadores de Plasminogênio/metabolismo , Enfisema Pulmonar/diagnóstico , Fumar/efeitos adversos , Adulto , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/etiologia , Testes de Função Respiratória , Tomografia Computadorizada por Raios XRESUMO
STUDY OBJECTIVE: To determine the effect of exposure to cigarette smoke on the elastolytic activity of guinea pigs' alveolar macrophages (AMs), and to compare elastolytic activity of AMs obtained by BAL with that of lung macrophages (LMs) obtained from minced lung tissue. METHODS: AMs were obtained by BAL from seven adult guinea pigs exposed to cigarette smoke for 5 d/wk during 6 weeks, as well as from age-matched control guinea pigs. From each animal, one lung was used to obtain LMs by mincing and teasing the lung, followed by enzymatic digestion and isolation of mononuclear cells by Hypaque-Ficoll separation. The other lung was inflated and fixed to quantitate emphysema by the destructive index (DI). Elastolytic activity (microgram of elastin degraded by 10(6) macrophages) was determined at 24, 48, and 72 h, by culturing AMs and LMs (1 x 10(6) cells in 1 mL of medium) in 3H-elastin-coated wells. RESULTS: In animals exposed to cigarette smoke, the total number of BAL cells (8.6+/-2.1 x 10(6)) and DI (21.8+/-8.1) were significantly higher than in nonexposed animals (6.4+/-1.8 x 10(6), p<0.05 for cells, and 12.1+/-4.1, p<0.01 for DI). Elastolytic activity of AMs from smoke-exposed guinea pigs was significantly higher at 24, 48, and 72 h than elastolytic activity of AMs from control animals (19.0+/-9.4 vs 10.0+/-5.3, p<0.05 at 72 h). Likewise, elastolytic activity of LMs was significantly higher in exposed than nonexposed guinea pigs (11.8+/-7.7 vs 7.4+/-5.0 at 72 h, p<0.05). Elastolytic activity of LMs was not significantly different from elastolytic activity of AMs, both in exposed guinea pigs (11.8+/-7.7 vs 19.0+/-9.4 at 72 h) and nonexposed animals (7.4+/-5.0 vs 10.0+/-5.3 at 72 h). CONCLUSIONS: These results indicate that elastolytic activity of both AMs and LMs of guinea pigs increases significantly after exposure to cigarette smoke and that AMs and LMs have similar elastolytic activities.
Assuntos
Elastina/metabolismo , Macrófagos Alveolares/metabolismo , Enfisema Pulmonar/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Cobaias , Pulmão/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Macrófagos Alveolares/patologia , Enfisema Pulmonar/patologiaRESUMO
The severity of pulmonary fibrosis is the main prognostic factor for survival of patients with interstitial lung diseases (ILD). Unfortunately, lung biopsy, which is the best method to assess fibrosis quantitatively, is done only once during the evolution of the disease. In this study we analyzed the relationship between the degree of fibrosis and the exponential constant k, derived from the lung pressure-volume curve (LPVC) in 33 patients with chronic ILD, 19 with pigeon breeder's disease (PBD), and 14 with idiopathic pulmonary fibrosis (IPF). Pulmonary function tests, including the LPVC, were obtained before biopsy. A semiquantitative histologic assessment of the severity of fibrosis was performed on lung tissues. All patients showed a decrease of total lung capacity, residual volume, compliance, and Pao2. The mean value of the constant k was 0.08 +/- 0.06. When expressed as a percent of normal values, 25 patients exhibited values of k lower than 70% of predicted; of the remaining 8 patients whose values were above 70% of predicted, 7 had PBD and only one IPF. On morphologic analysis, 19 patients displayed more than 50% fibrosis. No significant correlations were found between the extent of the lesion or severity of lung fibrosis and the conventional pulmonary function tests. By contrast, a moderate but significant correlation was found between k and the severity of lung fibrosis (r = -0.38, p < 0.05). These findings show that the shape of the LPVC, represented by the constant k, predicts the degree of lung fibrosis and could be useful in the clinical assessment and follow-up of patients with ILD.
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Fibrose Pulmonar/fisiopatologia , Adolescente , Adulto , Idoso , Biópsia , Feminino , Humanos , Complacência Pulmonar/fisiologia , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/patologiaRESUMO
Digital clubbing is a common sign in a variety of lung diseases. Although its pathogenesis remains unclear, it is known that the degree of clubbing might vary and even disappear, particularly when the underlying disease is a malignant neoplasm that has been removed. By contrast, because of the short expectancy of life in patients with pulmonary fibrosis, it is unusual to observe regression of clubbing. In this work, we report a case of reversible clubbing after lung transplantation.
Assuntos
Transplante de Pulmão , Osteoartropatia Hipertrófica Secundária/fisiopatologia , Adulto , Humanos , Masculino , Osteoartropatia Hipertrófica Secundária/etiologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/cirurgiaRESUMO
To determine the acute effect of smoking on DLCO, we studied 12 smokers (mean age, 36 yr; range, 19 to 52 yr, six men and six women) before and after they had smoked as many cigarettes as they could (mean, 6.0; SD, 1.9) over a period of 1 h. Blood COHb was estimated using a rebreathing-breathholding technique after a vital capacity inhalation of O2. Capillary blood volume (VC) was determined from DLCO performed at inspired O2 concentrations of 25 and 90%. DLCO (in ml/min/mm Hg) corrected for COHb back pressure decreased from 22.5 (SD, 6.6) before smoking to 21.0 (SD, 6.6) after smoking (p = 0.003). After correction for the "anemia effect" of COHb, DLCO still significantly decreased, from 22.8 (SD, 6.3) before smoking to 21.8 (SD, 6.4) after smoking p = 0.01). VC (corrected for the reduction in hemoglobin by COHb) was 52.0 (SD, 20.1) ml before smoking and 46.4 (SD, 22.7) ml after smoking; this difference did not achieve statistical significance (p = 0.056). There was no significant change in DLCO or VC in six control subjects tested before and after 1 h of sham smoking of an unlit cigarette. In 12 control subjects studied before and after inhalation of 0.1% CO to result in mean COHb levels of 10.6% (SD, 1.4%), there was a slight but significant decrease in VC (mean change, 21%) and in DLCO (mean change, 4%) after correction for COHb back pressure and reduction in available hemoglobin, suggesting that CO inhalation may have a direct effect on DLCO by reducing VC.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Monóxido de Carbono/metabolismo , Capacidade de Difusão Pulmonar/fisiologia , Fumar/efeitos adversos , Adulto , Carboxihemoglobina/metabolismo , Feminino , Humanos , Pulmão/irrigação sanguínea , Masculino , Microcirculação/fisiologia , Fumar/fisiopatologia , Espirometria , Capacidade Vital/fisiologiaRESUMO
We studied 16 smokers, with a mean age of 41 yr (SD, 12 yr) and a mean DLCO of 81% predicted (SD, 19%), before and after smoking cessation. Two subjects were able to stop smoking for only 24 h, whereas 14 subjects abstained for 1 wk, 11 for 1 month, and five for 3 months. The initial mean DLCO in ml/min/mm Hg was 18.9 (SD, 4.6) after correction for COHb back pressure and the reduction in hemoglobin because of COHb. A week after smoking cessation there was a significant increase in DLCO, to 20.8 (SD, 5.4), p = 0.001. There was no further increase in DLCO at 1 month or at 3 months. In four subjects tested while they were still smoking and 24 h after smoking cessation, there was a significant increase in DLCO after correction for COHb, from 17.4 (SD, 1.5) to 19.8 (SD, 1.3), p = 0.02. These results indicate that after smoking cessation there is a rapid improvement in DLCO, suggesting that smoking had previously decreased DLCO. However, there may also be an irreversible component to the reduction of DLCO in some of the subjects in whom the DLCO remained abnormal even after continued smoking cessation for 1 month.