Level of asthma control and healthcare utilization in Latin America.

The purpose of this study was to investigate whether uncontrolled asthma was associated with healthcare outcomes among Latin American patients with asthma. We used data from 2168 patients with asthma who participated in the 2011 Latin America Asthma Insights and Management (AIM) survey. Using Global Initiative for Asthma (GINA) guidelines, patients were categorized as having asthma that was well-controlled, partly controlled, or uncontrolled. Overall, 7% of the patients surveyed had asthma that was classified as well-controlled. Patients whose asthma was not well-controlled were significantly more likely to report use of asthma medications (ORs ranging from 1.6-41) and to have had emergency healthcare visits or hospitalizations for their asthma in the previous year (ORs ranging from 2.1 to 5.9). They also reported decreases in their productivity compared to patients with well-controlled asthma. These associations suggest that emphasis on improving asthma control could have substantial effects on patient productivity and utilization of healthcare resources.

Prolonged-release pirfenidone in patients with pulmonary fibrosis as a phenotype of post-acute sequelae of COVID-19 pneumonia. Safety and efficacy.

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.

Cell proliferation kinetics and genotoxicity in lymphocytes of smokers living in Mexico City.

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.

Clubbing in hypersensitivity pneumonitis. Its prevalence and possible prognostic role.

To know the prevalence and prognostic significance of finger clubbing in hypersensitivity pneumonitis induced by avian antigen, this physical sign was evaluated in 82 patients who were followed up from 1 to 5 years (mean, 2.6 years). According to clinical, roentgenographic, and functional criteria, the patients were classified in one of three stages at admission as well as at least 1 year later. Digital clubbing was retrospectively recorded as present or absent by physical examination. Our results showed that 44 patients (51%) included in this study presented clubbing at the time of diagnosis. Sixteen of these patients presented with worsening of their lung disease, whereas only 5 of the 38 patients without clubbing incurred a worsening of their condition. This finding suggests that digital clubbing is frequent in pigeon breeder's disease and may help to predict clinical deterioration.

Evaluation of cardiac output by thoracic electrical bioimpedance during exercise in normal subjects.

We compared cardiac output determined simultaneously by two methods, the CO2 rebreathing technique and the thoracic electrical bioimpedance method (Bomed NCCOM-3 equipment). The studies were performed in duplicate in 11 healthy male subjects at rest and during three levels of steady-state exercise on a cycle ergometer at 60, 120, and 180 W. Cardiac output at 60 and 120 W was slightly lower (p less than 0.01) by the thoracic impedance method (12.2 +/- SE 2.2 and 15.7 +/- SE 3.5 L/min, respectively) than by the CO2 rebreathing method (14.0 +/- SE 2.1 and 17.9 +/- SE 3.0 L/min, respectively), suggesting a systematic bias between the two methods of measurement. However, if allowance is made for that bias, there would be acceptable agreement between the two methods at 60 and 120 W. Although the results were not significantly different between the two methods at rest and at 180 W, there was no acceptable agreement between the two methods probably because the CO2 rebreathing method at rest was more liable to show error due to the small arteriovenous CO2 difference, while the impedance method was less reliable at 180 W. Cardiac output by both methods correlated with O2 consumption, with the correlation being higher for cardiac output by the rebreathing method (r = 0.94) than for thoracic impedance (r = 0.88). The results suggest that the thoracic electrical bioimpedance method can be used for determination of cardiac output during mild or moderate levels of exercise in normal subjects.

Exponential analysis of the lung pressure-volume curve in patients with chronic pigeon-breeder's lung.

Pigeon-breeder's lung (PBL) is extremely common in Mexico City and often progresses to irreversible pulmonary fibrosis. The exponential analysis of the lung pressure-volume (PV) curve (V = A - Be-kp) has been suggested as a method to separate the lung restriction caused by inflammation from that caused by pulmonary fibrosis; a significantly decreased value for the exponential constant, k, suggests a change in the mechanical properties of the functioning lung parenchyma, while a normal value accompanied by restriction suggests subtraction of lung units without a change in the mechanical properties of the functioning units. We measured lung volumes and static PV curves in 29 patients who had persistent lung restriction following a biopsy-proven diagnosis of PBL. Mean values in the 29 subjects were as follows: age, 43 +/- 13 years; TLC, 61 +/- 15 percent of predicted; VC, 46 +/- 19 percent of predicted; and k, 55 +/- 17 percent of predicted. Twenty-four of the 29 patients had values for k that were below the 95 percent confidence level, and five had "normal" values. There was no difference in TLC and VC (percent of predicted) between those with or without a decreased value for k. Four of five patients with a normal value for k improved subsequent to diagnosis, while only one of 21 patients with a decreased k improved. We conclude that increased lung elasticity manifested by a low value for k is common in patients with chronic PBL. These results support the observation of frequent irreversible lung fibrosis in these patients. Measurements of k could prove a good prognostic indicator at the time of initial diagnosis.

Relationship of alveolar macrophage plasminogen activator and elastase activities to lung function and CT evidence of emphysema.

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.

Colchicine, D-penicillamine, and prednisone in the treatment of idiopathic pulmonary fibrosis: a controlled clinical trial.

STUDY OBJECTIVE: We compared the long-term efficacy of the combination of colchicine and/or D-penicillamine with prednisone, in comparison to prednisone alone in patients with idiopathic pulmonary fibrosis (IPF). DESIGN: Nonrandomized prospective study in patients with IPF confirmed by biopsy specimen. SETTING: National Institute of Respiratory Diseases, Mexico. PATIENTS: Fifty-six IPF patients were included in this study. Patients received either colchicine/ prednisone (n=19), D-penicillamine/prednisone (n=11), D-penicillamine/colchicine/prednisone (n=11), or prednisone alone (n=15). Prednisone therapy was started at 1.0 mg/kg/d for 1 month followed by a biweekly taper to a maintenance dose of 15 mg/d. Colchicine was administered at a daily dose of 1.0 mg, and D-penicillamine was given at a daily dose of 600 mg. MEASUREMENTS AND RESULTS: Response to therapy was assessed by changes in lung function test results as measured by total and vital lung capacities, arterial blood gas analysis at rest breathing room air, and survival. No significant differences either in lung mechanics or in arterial gases were found in any group relative to the baseline measurement. Thirteen of the 56 patients died during the first 2 years, and 29 were dead at 5 years follow-up. Comparison of survival curves by Cox regression model showed no statistically significant difference among the four groups. Known side effects attributable to prednisone were more common and severe than those attributable to the other drugs. CONCLUSIONS: Our results suggest that neither colchicine nor D-penicillamine modified the progressive course of prednisone-treated IPF, and that the search for new drugs is imperative.

Collagenase and collagenase inhibitors in bronchoalveolar lavage fluids.

Collagenase, collagenolytic activity and tissue inhibitor of metalloproteinases were evaluated in bronchoalveolar lavage from 25 patients with hypersensitivity pneumonitis and four control subjects. Patients were followed between two and three years, after which they were classified as "healed," "improved," or "worsened." In control samples, immunoreactive collagenase was not detected. The enzyme was present in four of seven patients who healed, six of ten patients who improved, and four of eight patients who worsened. There was no relationship between the presence or absence of BAL collagenase or its concentration and the evolution of the disease. Latent collagenolytic activity was detected only in 5 of the 14 patients who displayed immunoreactive collagenase. Regarding collagenase inhibitor, TIMP was present in BAL fluid from all patients and normal subjects. Although the highest values were found in two cases who healed or improved, there was not a statistically significant difference among the three groups of patients, neither between patients nor control subjects. These findings suggest that at least in HP, the presence of collagenase, collagenolytic activity, or TIMP in BAL fluid is not associated with the prognosis of the disease.

Effect of exposure of guinea pigs to cigarette smoke on elastolytic activity of pulmonary macrophages.

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.

Reversal of digital clubbing after lung transplantation.

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.

Effect of assay conditions on measurement of elastolytic activity of alveolar macrophages in culture and characterization with proteinase inhibitors.

We have investigated whether varied assay conditions account for the conflicting reports on measured elastolytic activity of alveolar macrophages (AM) cultured in direct contact with the 3H-elastin substrate coated onto 16-mm wells in serum-containing media. The data indicate that measured elastolytic activity in this assay system was dependent on the amount of 3H-elastin/culture well. 3H-elastin > 350 micrograms/well, in contrast to the < or = 200 micrograms/well commonly used in this assay system, resulted in optimal measurement of elastolytic activity that was linear with respect to culture time (up to 72 h examined) and was directly proportional to number of AM/well (up to 1.0 x 10(6) examined). The sensitivity of measured elastolytic activity to tissue inhibitor of metalloproteinases (TIMP) and to Z-phe-phe (a specific cysteine proteinase inhibitor) was not affected by amount of 3H-elastin/well, but appears to be dependent on the time period of AM culture. TIMP (at 5 microM, maximal dose examined) inhibited the measured elastolytic activity by 25% in 24-h cultures compared to 69% in 72-h cultures; Z-phe-phe (at 10 microM, dose at which maximal effect was obtained) inhibited the elastolytic activity by 45% in the 24-h cultures compared to 34% in the 72-h cultures. These findings indicate that differences in substrate levels and in culture time have a significant effect on the results obtained in measurement of AM-mediated elastolytic activity in culture, which may account for the conflicting reports in the literature. Thus standard optimal assay condition are required for valid interpretation of results of AM-mediated elastolytic activity measurements.

[Severity of dyspnea during exercise: similarities and differences between patients with COPD or pulmonary fibrosis]. / Similitudes y diferencias en el grado de disnea durante el ejercicio en pacientes con EPOC y fibrosis pulmonar.

To understand the mechanisms leading to dyspnea during exercise and to identify possible predictive factors, we compared dyspnea at rest (baseline)and during exercise in 27 patients with chronic obstructive pulmonary disease (COPD) and 39 pulmonary fibrosis (PF) patients. We also compared spirometry and blood gases at rest and after exercise,which consisted of a 12-minute walking test (12 WT). Heart rate and oxygen saturation (SaO2) were recorded every two minutes during the 12 WT. Distance walked was also recorded. Although dyspnea changed during the 12 WT in both groups (p < 0.001),the maximum level of dyspnea reached in the two groups was not statistically different. COPD patients walked farther than did PF patients (782 +/- 182 m vs. 618 +/- 225 m, respectively;p = 0.002) and paused less often during the 12 WT than did PF patients(0.18 +/- 0.55 vs. 0.82 +/- 1.55, respectively; p <0.05). After adjusting for diagnosis, age, sex, baseline dyspnea,distance walked and pauses during the 12 WT, we found that only SaO2 was significantly related to severity of dyspnea during exercise. We conclude that there are important differences in degree of dyspnea experienced during exercise by COPD and PF patients and that SaO2 is the only variable that predicts severity of dyspnea.

[Smoking among Mexican physician. A comparative analysis with smokers who are not physicians]. / Tabaquismo en médicos mexicanos. Un análisis comparativo con fumadores que no son médicos.

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.

[Capability of clinical and laboratory findings to predict the grade of fibrosis and the diagnosis in diffuse interstitial lung diseases]. / Capacidad de clínica y laboratorio para predecir el grado de fibrosis y el diagnóstico en enfermedades pulmonares intersticiales difusas.

Our objective was to assess the capacity of clinical and laboratory information to predict findings in the lung biopsy in interstitial lung diseases (ILD). We studied 121 patients with ILD as a cohort recruited in our institute from 1983 to 1987 with the diagnosis of hypersensitivity pneumonitis (HP) and usual interstitial pneumonia (UIP). Histologic diagnosis (HP vs UIP) and degree of fibrosis (< 50% of the biopsy surface vs > or = 50%) were used as the gold standard to compare a series of clinical and laboratory variables in the initial assessment. We used a stepwise logistic regression model to predict the biopsy results. The model was calculated in half of the patients selected by random sampling, and the calculated model was tested in the other half of the patients. Variables found to predict degree of fibrosis were (with relative risk RR and 95% confidence interval): a radiographic pattern of honeycombing (RR 5.0 from 0.9-29), digital clubbing (RR 8 from 1.4-48) and gender (RR 2.9 from 0.4-20). This model classified correctly 72% of the biopsies, with a sensitivity of 0.38, a specificity of 0.85 and a kappa of 0.25 +/- 0.19 (p = 0.17 NS). For histologic diagnosis (NIU vs NH), the model included gender (RR 6.6, 1.3-33), honeycombing (RR 1.6, from 0.4-6.0), digital clubbing (RR 4.6, from 1.2-18), and vital capacity expressed as percent of predicted (RR 0.96, from 0.92-1.00).(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of circulating miRNAs profiles that distinguish malignant pleural mesothelioma from lung adenocarcinoma.

Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging. Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly difficult, yet clinically important since the two neoplasias call for different treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be used to distinguish MPM from AD has not been reported. We conducted a wide screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD patients (N = 36), and healthy subjects (N = 45) to identify non-invasive biomarkers for differential diagnosis of MPM and AD, using deep sequencing. Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were upregulated in AD compared to healthy controls. Of these, eight were distinctive for AD and three were unique for MPM. Direct comparison of the miRNA profiles for MPM and AD revealed differences in miRNA levels that could be useful for differential diagnosis. No differentially expressed novel miRNAs were found. Further bioinformatics analysis indicated that three upregulated miRNAs in MPM are associated with the p38 pathway. There are unique alterations in serum miRNAs in MPM and AD compared to healthy controls, as well as differences between MPM and AD profiles. Differing miRNA levels between MPM and AD may be useful for differential diagnosis. A potential association to p38 pathway of three upregulated miRNAs in MPM was revealed.