The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos.

BACKGROUND: Leukotrienes play an important role in allergic and inflammatory diseases, but reports on the involvement of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) in asthma have been inconclusive. OBJECTIVE: To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans. METHODS: The LTA4H gene was sequenced in individuals from both groups to identify novel polymorphisms. Single-nucleotide polymorphisms (SNPs) in the ALOX5AP and LTA4H genes were analysed for associations with asthma and asthma-related phenotypes in 687 parent-child trios of Mexican and Puerto Rican origin. RESULTS: In LTA4H, five previously unknown polymorphisms were identified. Two SNPs within LTA4H (rs17525488 and rs2540493) were protective for asthma in Latinos (P=0.007 and 0.05, respectively). Among the Mexican patients, LTA4H polymorphisms were associated with baseline lung function and IgE levels. For ALOX5AP, the minor allele at SNP rs10507391 was associated with protection from asthma (odds ratio=0.78, P=0.02) and baseline lung function (P=0.018) in Puerto Ricans. A gene-gene interaction was identified between LTA4H (rs17525488) and ALOX5AP (rs10507391), (P=0.003, in the combined sample). CONCLUSION: Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations.

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.

Prevalence of high hematocrits in patients with interstitial lung disease in Mexico City.

Erythrocytosis, a known response to chronic hypoxemia, is considered infrequent in interstitial lung diseases. We studied the prevalence of high hematocrit (Hct) values and the relationship between Hct and SaO2 in 79 patients with chronic pigeon breeder's lung (PBL) and 34 with idiopathic pulmonary fibrosis (IPF), all of whom lived in the Mexico City metropolitan area (2,240 m above sea level). Lung biopsy was performed in 31 patients with IPF and 71 with PBL. We analyzed only one simultaneous measurement of Hct and SaO2 per patient (usually the initial measurement) before treatment. No additional cause for anemia or erythrocytosis was detected. Forty-eight percent of the patients with PBL (38/79) and 62 percent of those with IPF (21/34) had high Hct values (greater than 2 SD above mean values for Mexico City); in 14 (12.3 percent) of the 113 patients (nine with PBL and five with IPF), the Hct was above 60 percent. The Hct and SaO2 values displayed a poor correlation for the whole group: Hct = 65.7-0.16(SaO2), r = 0.24, p = 0.012. The correlation between Hct and SaO2 was nonsignificant if patients were separated by diagnosis. For an SaO2 of less than 80 percent, the slope of SaO2 vs Hct was zero. Half of our patients with PBL and IPF had Hct values that were high for the altitude. In most cases, Hct responses fell within the confidence limits reported as normal at high altitudes. We found a poor relationship between Hct and awake SaO2.

Lung collagen metabolism and the clinical course of hypersensitivity pneumonitis.

We studied lung collagen metabolism in 18 patients with hypersensitivity pneumonitis to determine if changes at this level could explain the different clinical courses followed by these patients. Collagen concentration, biosynthesis and degradation were measured in lung tissue samples obtained before treatment. Four patients healed, eight improved and six did not improve or worsened. All patients who healed showed an important increase in collagenolysis; patients who improved had normal or high values, but significantly less than those obtained in patients who healed. Finally, five out of the six patients who did not improve or worsened had a significant decrease in degradation. These findings support the notion that a diminution of local collagenolysis may play a role in the progression to fibrosis in some patients with hypersensitivity pneumonitis and can also be a useful tool to predict the prognosis of this disease.

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.

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.

Rating of breathlessness at rest during acute asthma: correlation with spirometry and usefulness of breath-holding time.

We studied 13 patients with acute attacks of asthma to test the hypothesis that magnitude of dyspnea at rest correlates well with spirometry and with breath-holding time. Dyspnea ("falta de aire" in Spanish) was quantitated with a linear numerical scale from 0 to 10. We measured breath-holding time, breathing frequency (f), and FEV1 and FVC both expressed as percent of normal. Measurements were done on the patient's arrival and were repeated 3 to 6 times until dyspnea at rest disappeared or was minimal. Dyspnea magnitude, f, and breath-holding time correlated well with FEV1% and FVC% (r between 0.65 and 0.78), and better with changes in FEV1% and FVC% with respect to initial values (delta FEV1 y delta FVC; r between 0.80 and 0.89). Breath-holding time and f changed in proportion to magnitude of dyspnea (r = -0.85 and 0.87 respectively). Regression equations were: dyspnea = 6.34 -0.16 (delta FEV1) r = 0.80, and dyspnea = 7.82-0.105 (FEV1%) r = 0.62. Using multiple regression we improved prediction of FEV1% with easily obtained variables (R = 0.76). These results suggest that: 1) magnitude of dysnea, f, and breath-holding time correlate with severity of airflow obstruction in acute asthma attacks associated with dyspnea at rest; and 2) breath-holding time varies inversely with dyspnea magnitude when it is present at rest.

[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)

[Hiatal hernia in asthmatic patients: prevalence and its association with gastroesophageal reflux]. / La hernia hiatal en pacientes asmáticos: prevalencia y su asociación con reflujo gastroesofágico.

INTRODUCTION: Evidence of a high prevalence of hiatal hernia (HH) and gastroesophageal reflux (GER) in asthmatic patients has been found. However, the relationship between these entities has not been studied in our country. OBJECTIVES: 1) To inform the prevalence of hiatal hernia in asthmatic patients, 2) To compare the prevalence of hiatal hernia in asthmatic vs. non-asthmatic patients, 3) To establish a possible association between hiatal hernia and GER in asthmatic patients. MATERIALS AND METHODS: In order to detect and to compare the prevalence of hiatal hernia in asthmatic and non-asthmatic patients, upper gastrointestinal endoscopy was performed. To establish the association between asthma and GER, data obtained from a gastrointestinal symptoms questionnaire, an esophageal manometry and an ambulatory pH recording in asthmatics with or without hiatal hernia were compared. RESULTS: Hiatal hernia was more frequently observed in asthmatics than in non-asthmatics (62% vs. 34%, p = 0.02). The frequency of typical symptoms of GER was similar in both asthmatics with or without hiatal hernia (54 vs. 43%, p = 0.3). Lower esophageal sphincter incompetence was similar in asthmatics with hiatal hernia (35%) vs. asthmatics without hiatal hernia (22%), as detected by manometry. Pathological GER was diagnosed by pH recording in 81% of the asthmatics with hiatal hernia and in 65% of asthmatics without hiatal hernia (p = 0.1). CONCLUSIONS: There is a high prevalence of hiatal hernia in asthmatics, which in turn results to be greater than in non-asthmatic patients. The presence of hiatal hernia does not correlate with the detection of pathological GER as determined by pH recording in this group of patients.

[Gastroesophageal reflux in asthmatic patients: an incidence study and clinical correlation]. / El reflujo gastroesofágico en pacientes asmáticos: estudio de frecuencia y correlación clínica.

The prevalence of gastroesophageal reflux (GER) in asthmatic patients is elevated, but the exact frequency remains unknown. The relationship between GER and asthma has not been investigated in Mexico. The objective of this study is to know the frequency of GER in Mexican asthmatic patients and the possible relationship with the severity of asthma. Fifty patients with adult-onset asthma were studied. AII of them fulfill the diagnostic criteria of the National Institutes of Health, U.S. The evaluation included a symptoms questionnaire, spirometry, esophageal manometry, 24-h esophageal pH-recording, and an upper gastrointestinal endoscopy. Twenty-three patients had mild asthma (46%), 16 moderate (32%) and 11 had severe asthma (22%). Twenty-seven (54%) reported heartburn and regurgitation at least twice a week. The esophageal pH-recording showed pathologic GER in 37 subjects (74%) and endoscopic esophagitis was found in 7 cases (14%). The pH-recording showed pathologic GER in 13 patients with mild asthma (57%), in 13 with moderate asthma (81%) and in all patients with severe asthma (100%). The frequency of GER in Mexican asthmatic patients is high and increases proportionately with the severity of asthma. This factor must be considered in the integral evaluation of these patients.

[Comparative study of the effectiveness of 2 oral corticoids in the control of severe crisis of bronchial asthma: deflazacort and prednisone]. / Estudio comparativo de la eficacia de dos corticoides orales en el control de la crisis grave de asma bronquial: deflazacort y prednisona.

This article contains the results reached after conducting a study with 30 patients hospitalized or seen at the Emergency Ward of the National Institute of Respiratory Diseases, diagnosed as suffering from a severe bronchial asthma crisis, in whom the crisis was controlled with conventional measures. The purpose of this study was to compare the efficacy of deflazacort and prednisone as anti-inflammatory agents capable of controlling severe asthma crisis in addition to analyzing their side effects. Deflazacort showed to be as effective as prednisone.

D-penicillamine in the therapy of fibrotic lung diseases.

We studied 12 patients with pulmonary fibrosis treated with D-Penicillamine in an attempt to regulate the collagen metabolism that is seriously affected in this group of patients. After six years follow-up we found a 33% survival rate compared to a 5% survival rate in patients treated with corticosteroids (p less than 0.01). Functional respiratory tests as well as quality of life were improved in all patients. No side effects attributable to D-Penicillamine were detected probably due to the fact that we used smaller doses than those reported in the treatment of other diseases of the connective tissue. We conclude that D-Penicillamine can be a useful alternative drug in the therapy of patients with pulmonary fibrosis.

Concentration, biosynthesis and degradation of collagen in idiopathic pulmonary fibrosis.

Despite several studies both in vitro and in vivo, the pathogenesis of pulmonary fibrosis is unclear and some findings related to the biochemistry of collagen are controversial. Collagen metabolism was studied in 11 patients with idiopathic pulmonary fibrosis and in six control subjects. There was an increase in collagen concentration (mean 327 (SD 76) compared with control values of 185 (18) micrograms/mg dry weight, p less than 0.001), normal values for biosynthesis (mean 2.2% (0.8%) v 2.08% (0.5%), and a noteworthy decrease in collagenolytic activity (mean 0.07 (0.04) v 0.23 (0.04) micrograms of collagen degraded per mg of collagen incubated, p less than 0.001). These results suggest that an alteration in enzymatic breakdown of collagen plays an important role in the maintenance and progression of interstitial fibrosis in this disease.

[Normal values of alpha 1 antitrypsin in the mestizo Mexican population]. / Valores normales de alfa 1 antitripsina en población mestiza mexicana.

Serum levels of alpha 1 antitrypsin (AAT) were determined in 100 mestizo individuals from Mexico. They were selected among those whose ancestors lived in Mexico at least for three generations, no clinical incidence of acute or chronic disease. Concentration ranged from 57-148 UI/ml and are lower than those reported in the literature. No age or sex differences were found. A total of 95% of the population fall between 68-136 UI/ml.

Subpopulations of T cells in lung biopsies from patients with pigeon breeder's disease.

Monoclonal antibodies were used to determine surface phenotypes of T cells in tissue obtained by open lung biopsies from patients with chronic hypersensitivity pneumonitis (pigeon breeder's disease). The results indicate that an increased number of suppressor/cytotoxic cells is present in these patients when compared with the number of helper/inducer cells. These findings, which were present within the interstitium, are consistent with those found in bronchoalveolar lavage of patients with this disease. In addition, in two-thirds of the patients there was a greater total number of helper and suppressor cells than the total count for Pan T cells. A possible interpretation of these findings might be the presence of both markers in the same cell.

Immunoregulatory abnormalities in patients with pigeon breeder's disease.

T-cell suppression induced by concanavalin-A (Con-A) and the prostaglandin suppressor system (PSS) were studied in 14 patients with pigeon breeder's disease (PBD), 12 and 10 asymptomatic breeders, and 8 controls. Our results showed that PBD patients display a significant decrease in T-cell-induced suppression (29.6 +/- 15.3% vs. 61.2 +/- 9.3% in controls p less than 0.05); whereas asymptomatic breeders respond heterogeneously: 5 showed decreased suppression and 7 were within the normal range obtained in controls. In contrast, the patients presented a higher PSS index compared with the other 2 groups, suggesting an inverse relationship between the 2 systems. These findings indicate that there are relevant differences between PBD patients, asymptomatic breeders, and normal subjects in some immune interactions, which may at least partially explain the characteristic cellular and humoral hyperreactivity observed in patients with this disease.

[Effect of pregnancy and the puerperium on the development of extrinsic allergic alveolitis]. / Influencia del embarazo y puerperio en el desarrollo de la alveolitis alérgica extrínseca.

Extrinsic Allergic Alveolitis (EAA) is a disease characterized by an exaggerated immune response to inhaled organic dusts that can result in alveolar, and occasionally bronchiolar, damage. This damage can disappear completely with the elimination of the antigen and/or treatment with anti-inflammatory agents. Nonetheless, an important group of these patients do not improve; the inflammatory reaction persists. With time, this results in the deposit of abnormal connective, tissue with respect to its quantity and quality, in the pulmonary interstitium destroying the normal parenchymal architecture and making gas exchange impossible. The most common cause of this disease is inhalation of pigeon antigen with a 5:1 predominance in women. Pregnancy has been considered as a case of allotransplantation that produces in the mother a relative hyporeactive condition. In modifying the immune response to the fetus, it is also modified to other foreign antigens. In this work, we studied 80 cases of EAA, 67 females and 13 males. Of the 67 women, 11 (17.1%) presented with the disease after delivery. Symptoms began from 5 days to 7 months after delivery. Eight of the 11 women had been in contact with the antigen before the beginning of the pregnancy without showing symptoms until after delivery. In 4 cases, there had been contact with the antigen in other pregnancies, without symptoms. EAA is a disease involving the immune system in which changes can be seen in its development during pregnancy, as is also seen in other immune diseases, such as Lupus Erythematosus, Rheumatoid Arthritis and other connective tissue diseases. During pregnancy, the mother becomes tolerant. There is a decrease in non-self recognition.(ABSTRACT TRUNCATED AT 250 WORDS)

Exposure to biomass smoke and chronic airway disease in Mexican women. A case-control study.

A case-control study was performed in women older than 40 yr of age to evaluate the risk of cooking with traditional wood stoves for chronic bronchitis and chronic airway obstruction (CAO). The subjects were recruited from patients attending a referral chest hospital in Mexico City. We selected 127 patients with chronic bronchitis or CAO, of which 63 had chronic bronchitis alone, 23 had CAO alone (FEV1 less than 75% of predicted), and 41 had both chronic bronchitis and CAO (cases). Four control groups were selected: 83 patients with pulmonary tuberculosis, 100 patients with interstitial lung diseases, 97 patients with ear, nose and throat ailments, and 95 healthy visitors to the hospital (controls). Exposure to wood smoke, assessed as any or none, and as hour-years (years of exposure multiplied by average hours of exposure per day) was significantly higher in cases than in controls. Crude odds ratios for wood smoke exposure were 3.9 (95% CI, 2.0 to 7.6) for chronic bronchitis only, 9.7 (95% CI, 3.7 to 27) for CAO plus chronic bronchitis, and 1.8 (95% CI, 0.7 to 4.7) for CAO only. Differences in exposure to wood smoke persisted after adjusting by stratification and logistic regression for age, income, education, smoking, place of residence, and place of birth. Risk of chronic bronchitis alone and chronic bronchitis with CAO increased linearly with hour-years of cooking with a wood stove; odds ratios for exposure to more than 200 hour-years compared with nonexposed were 15.0 (95% CI, 5.6 to 40) for chronic bronchitis only and 75 (95% CI, 18 to 306) for chronic bronchitis with CAO. The findings support a causal role of domestic wood smoke exposure in chronic bronchitis and chronic airflow obstruction.

Analysis of the relationships between environmental factors (aeroallergens, air pollution, and weather) and asthma emergency admissions to a hospital in Mexico City.

There have been several studies of the relationships between environmental factors, particularly air pollution, and attacks of asthma. Most of these studies have ignored the potential confounding effects of aeroallergens such as pollens and fungal spores. We report a statistical analysis of the relationships between emergency admissions for asthma to a hospital in Mexico City and daily average airborne concentrations of pollen, fungal spores, air pollutants (O3, NO2, SO2, and particulates) and weather factors. Asthma admissions had a seasonal pattern with more during the wet season (May-October) than the dry season (November-April). There were few statistical associations between asthma admissions and air pollutants for the three age groups studied (children under 15 years, adults, and seniors [adults over 59 years]) in either season. Grass pollen was associated with child and adult admissions for both the wet and dry seasons, and fungal spores were associated with child admissions during both the wet and dry seasons. The analysis was done with environmental data averaged over the day of admission and the 2 previous days. Our results suggest that aeroallergens may be statistically associated more strongly with asthma hospital admissions than air pollutants and may act as confounding factors in epidemiologic studies.