Efficacy of the FEV1/FEV6 ratio compared to the FEV1/FVC ratio for the diagnosis of airway obstruction in subjects aged 40 years or over

The present cross-sectional, population-based study was designed to evaluate the performance of the FEV1/FEV6 ratio for the detection of airway-obstructed subjects compared to the FEV1/FVC <0.70 fixed ratio test, as well as the lower limit of normality (LLN) for 1000 subjects ³40 years of age in the metropolitan area of São Paulo, SP, Brazil. After the exclusion of 37 (3.7 percent) spirometries, a total of 963 pre-bronchodilator (BD) and 918 post-BD curves were constructed. The majority of the post-BD curves (93.1 percent) were of very good quality and achieved grade A (762 curves) or B (93 curves). The FEV1/FEV6 and FEV1/FVC ratios were highly correlated (r² = 0.92, P < 0.000). Two receiver operator characteristic curves were constructed in order to express the imbalance between the sensitivity and specificity of the FEV1/FEV6 ratio compared to two FEV1/FVC cut-off points for airway obstruction: equal to 70 (area under the curve = 0.98, P < 0.0001) and the LLN (area under the curve = 0.97, P < 0.0001), in the post-BD curves. According to an FEV1/FVC <0.70, the cut-off point for the FEV1/FEV6 ratio with the highest sum for sensitivity and specificity was 0.75. The FEV1/FEV6 ratio can be considered to be a good alternative to the FEV1/FVC ratio for the diagnosis of airway obstruction, both using a fixed cut-off point or below the LLN as reference. The FEV1/FEV6 ratio has the additional advantage of being an easier maneuver for the subjects and for the lung function technicians, providing a higher reproducibility than traditional spirometry maneuvers.

Efficacy of the FEV1/FEV6 ratio compared to the FEV1/FVC ratio for the diagnosis of airway obstruction in subjects aged 40 years or over.

The present cross-sectional, population-based study was designed to evaluate the performance of the FEV1/FEV6 ratio for the detection of airway-obstructed subjects compared to the FEV1/FVC <0.70 fixed ratio test, as well as the lower limit of normality (LLN) for 1000 subjects (3)40 years of age in the metropolitan area of São Paulo, SP, Brazil. After the exclusion of 37 (3.7%) spirometries, a total of 963 pre-bronchodilator (BD) and 918 post-BD curves were constructed. The majority of the post-BD curves (93.1%) were of very good quality and achieved grade A (762 curves) or B (93 curves). The FEV1/FEV6 and FEV1/FVC ratios were highly correlated (r(2) = 0.92, P < 0.000). Two receiver operator characteristic curves were constructed in order to express the imbalance between the sensitivity and specificity of the FEV1/FEV6 ratio compared to two FEV1/FVC cut-off points for airway obstruction: equal to 70 (area under the curve = 0.98, P < 0.0001) and the LLN (area under the curve = 0.97, P < 0.0001), in the post-BD curves. According to an FEV1/FVC <0.70, the cut-off point for the FEV1/FEV6 ratio with the highest sum for sensitivity and specificity was 0.75. The FEV1/FEV6 ratio can be considered to be a good alternative to the FEV1/FVC ratio for the diagnosis of airway obstruction, both using a fixed cut-off point or below the LLN as reference. The FEV1/FEV6 ratio has the additional advantage of being an easier maneuver for the subjects and for the lung function technicians, providing a higher reproducibility than traditional spirometry maneuvers.

Chronic obstructive pulmonary disease is underdiagnosed and undertreated in São Paulo (Brazil): results of the PLATINO study.

Chronic obstructive pulmonary disease (COPD) is a common disease in adults over 40 years of age and has a great social and economic impact. It remains little recognized and undertreated even in developed countries. However, there are no data about its diagnosis and treatment in Brazil. The objectives of the present study were to evaluate the proportion of COPD patients who had never been diagnosed and to determine if the COPD patients who had been identified were receiving appropriate treatment. The Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) was a randomized epidemiological study of adults over 40 years living in five metropolitan areas, including São Paulo. The studied sample was randomly selected from the population after a division of the metropolitan area of São Paulo in clusters according to social characteristics. All subjects answered a standardized questionnaire on respiratory symptoms, history of smoking, previous diagnosis of lung disease, and treatments. All subjects performed spirometry. The criterion for the diagnosis of COPD was defined by a post-bronchodilator FEV1/FVC ratio lower than 0.7. A total of 918 subjects were evaluated and 144 (15.8%) met the diagnostic criterion for COPD. However, 126 individuals (87.5%) had never been diagnosed. This undiagnosed group of COPD patients had a lower proportion of subjects with respiratory symptoms than the previously diagnosed patients (88.9 vs 54.8%) and showed better lung function with greater FEV1 (86.8 +/- 20.8 vs 68.5 +/- 23.6% predicted) and FVC (106.6 +/- 22.4 vs 92.0 +/- 24.1% predicted). Among the COPD patients, only 57.3% were advised to stop smoking and 30.6% received the influenza vaccine. In addition, 82.3% did not receive any pharmacological treatment. In conclusion, COPD is underdiagnosed and a large number of COPD patients are not treated appropriately.

Chronic obstructive pulmonary disease is underdiagnosed and undertreated in São Paulo (Brazil): results of the PLATINO study

Chronic obstructive pulmonary disease (COPD) is a common disease in adults over 40 years of age and has a great social and economic impact. It remains little recognized and undertreated even in developed countries. However, there are no data about its diagnosis and treatment in Brazil. The objectives of the present study were to evaluate the proportion of COPD patients who had never been diagnosed and to determine if the COPD patients who had been identified were receiving appropriate treatment. The Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) was a randomized epidemiological study of adults over 40 years living in five metropolitan areas, including São Paulo. The studied sample was randomly selected from the population after a division of the metropolitan area of São Paulo in clusters according to social characteristics. All subjects answered a standardized questionnaire on respiratory symptoms, history of smoking, previous diagnosis of lung disease, and treatments. All subjects performed spirometry. The criterion for the diagnosis of COPD was defined by a post-bronchodilator FEV1/FVC ratio lower than 0.7. A total of 918 subjects were evaluated and 144 (15.8 percent) met the diagnostic criterion for COPD. However, 126 individuals (87.5 percent) had never been diagnosed. This undiagnosed group of COPD patients had a lower proportion of subjects with respiratory symptoms than the previously diagnosed patients (88.9 vs 54.8 percent) and showed better lung function with greater FEV1 (86.8 ± 20.8 vs 68.5 ± 23.6 percent predicted) and FVC (106.6 ± 22.4 vs 92.0 ± 24.1 percent predicted). Among the COPD patients, only 57.3 percent were advised to stop smoking and 30.6 percent received the influenza vaccine. In addition, 82.3 percent did not receive any pharmacological treatment. In conclusion, COPD is underdiagnosed and a large number of COPD patients are not treated appropriately.

Acute action of aminophylline in patients with amyotrophic lateral sclerosis.

OBJECTIVE: This study investigated whether aminophylline has an acute effect on the muscle performance of patients with amyotrophic lateral sclerosis (ALS). The study was a randomized, double-blind, crossover against placebo. MATERIALS AND METHODS: Twenty-five patients (48.5 +/- 14.1 years) with ALS were evaluated by means of forced vital capacity (FVC), maximal mouth inspiratory and expiratory pressures (P(Imax)/P(Emax)) and endurance, maximum voluntary ventilation (MVV) and handgrip strength (HS); variables were measured before and after the patients received an intravenous infusion of aminophylline or placebo. RESULTS: MVV (P<0.02) and HS of the right and left hands (P=0.05) increased after aminophylline infusion. There was a positive correlation between FVC and P(Imax) (r=0.80; P<0.05); between MVV and P(Imax) post-aminophylline, respectively (r=0.77; P<0.05). Serum aminophylline levels ranged from 5.3 to 10.5 microg/mL (mean 7.30). CONCLUSION: The acute administration of aminophylline improves the endurance of respiratory muscles and increases handgrip strength in patients with ALS.

Effects of exposure to benzodiazepine during fetal life.

Dysmorphism and mental retardation have been reported in 7 Swedish children born of mothers who had taken high doses of benzodiazepines regularly during pregnancy. To explore this association further, we examined benzodiazepine use during pregnancy in 104,000 women whose deliveries were registered by the US public health insurance system, Medicaid, during 1980-83. Fetal outcomes were assessed from the health claims profiles of their offspring, up to 6-9 years after delivery. 80 pregnant women had received 10 or more benzodiazepine prescriptions during the 4 years. Their records showed heavy general use of health care and frequent alcohol and substance abuse, and other disorders that could confound any effect of the benzodiazepines. For the 80 pregnancies, 3 intrauterine deaths were identified as well as 2 infants with congenital abnormalities whose curtailed records suggested neonatal death. Records of 64 surviving children could be linked to these 80 pregnancies whilst records for 11 apparent survivors could not be located. 6 of the 64 survivors had diagnoses consistent with teratogenic abnormalities. The high rate of teratogenicity after heavy maternal benzodiazepine use occurs with multiple alcohol and substance exposure and thus may not be due to benzodiazepine exposure.

Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors.

OBJECTIVE: Case reports of suspected adverse pregnancy outcomes associated with prenatal exposure to angiotensin-converting enzyme inhibitors, particularly oligohydramnios, prolonged neonatal anuria, and defects of ossification of the skull dome, prompted us to examine pregnancy outcome in a large cohort of pregnant women for whom complete drug exposure information was known. METHODS: We studied the prescribed drug exposure histories and pregnancy outcomes of all women aged 15-44 years enrolled in Tennessee Medicaid who delivered a live-born or stillborn infant between January 1, 1983 and December 31, 1988. RESULTS: Of the 106,813 women enrolled in Tennessee Medicaid who delivered either a live-born or stillborn infant during the study period, 19 were exposed to an angiotensin-converting enzyme inhibitor during pregnancy. All 19 women delivered live infants. Among the 19 newborns, one preterm infant had prolonged anuria necessitating dialysis and a second preterm infant had microcephaly and a large occipital encephalocele. CONCLUSIONS: These outcomes represent a systematic follow-up of all angiotensin-converting enzyme inhibitor-exposed pregnancies. Despite the small number of exposures, there were two outcomes previously linked to prenatal use of these drugs, suggesting that the absolute risk may be high. In light of these findings and the case reports of others, it is prudent to avoid the use of angiotensin-converting enzyme inhibitors in pregnancy.

Neonatal anuria with maternal angiotensin-converting enzyme inhibition.

The use of angiotensin-converting enzyme inhibitors as antihypertensives has increased rapidly since the introduction of captopril in 1981. Seven cases of neonatal renal failure have been reported in patients with exposure to angiotensin-converting enzyme inhibitors that continued to the time of delivery. Two cases resulted in death of the newborn; the other five patients recovered after peritoneal dialysis. Because the relative frequency of normal outcomes is unknown, these data are insufficient for incidence-rate estimates or risk/benefit analyses. However, given the potential neonatal morbidity and mortality associated with late-pregnancy exposure to angiotensin-converting enzyme inhibitors, alternative therapies in the third trimester should be given consideration. If these drugs must be used in this context, the clinician should be prepared to deal with renal failure and hypotension in the newborn. The Food and Drug Administration invites reports of adverse pregnancy outcomes associated with such exposure.

Morbidity and mortality among low birth weight infants exposed to an intravenous vitamin E product, E-Ferol.

In April 1984, the US FDA was notified of an unusual clinical syndrome consisting of ascites, liver and renal failure, thrombocytopenia, and death among low birth weight infants exposed to an intravenous vitamin E preparation, E-Ferol. The product, which had not been tested for safety prior to marketing, was voluntarily withdrawn from the market in early April. To further investigate the reported associations, the FDA conducted a retrospective cohort study among seven neonatal intensive care units where the product had been used. Standardized abstraction forms were completed for infants admitted to a unit between Nov 1, 1983, and April 30, 1984. Included in the study were 379 infants weighing 2,000 g or less and surviving at least two days; 148 (39%) had been exposed to E-Ferol. Compared with the unexposed infants, the exposed infants were more likely to die and to have ascites, hepatomegaly, thrombocytopenia, and a combination of clinical events similar to the syndrome initially reported. We conclude that the use of E-Ferol in these neonatal intensive care units was associated with increased morbidity and mortality among exposed infants.

Pregnancy outcomes after first-trimester vaginitis drug therapy.

Prescription frequencies in the first trimester were compared for miconazole, clotrimazole, nystatin, candicidin, aminacrine compounds, and metronidazole before deliveries involving congenital anomalies versus those not linked to congenital anomalies. Prescriptions before spontaneous abortions were compared with those in the first trimester of deliveries and with those before legal abortions. No statistically significant association was observed with any of these agents for the overall frequency of birth defects or for specific birth defects analyzed (cardiovascular defects, oral clefts, and spina bifida). Two hundred fifty miconazole exposures among 4264 spontaneous abortions, compared with 2236 in the first trimester of 55,736 deliveries, provided an estimated relative risk of 1.4 (95% confidence limits 1.2-1.5). One hundred twelve treatments with clotrimazole among the spontaneous abortions, compared with 1086 among the deliveries, provided a relative risk of 1.4 (95% confidence limits 1.1-1.6). In contrast, large numbers of exposures to nystatin and aminacrine compounds did not show this association, suggesting that spontaneous abortions are caused by the imidazole agents miconazole and clotrimazole rather than the condition being treated. Because many associations were examined without previous hypotheses, and because the data were inadequate to show an elevated risk for clotrimazole when comparing spontaneous with legal abortion exposures, these findings are considered to be a signal for further studies rather than definitive in themselves.

Teratogen update: vitamin A congeners.

Despite animal vitamin A congener teratogenicity in animal studies since 1954, striking human findings only arose in 1983 following isotretinoin (ITR) marketing for oral treatment of severe acne. By November 1985, 44 outcomes with central nervous system (CNS), cardioaortic (CV), microtia, facial palsy, micrognathia, cleft palate, and/or thymic aplasia defects, and 33 spontaneous abortions have been reported. The critical period for exposure appears to be two to five weeks postconception, although this is clinically inexact. ITR half life is less than a day, although a teratogenic metabolite, 4-oxo-isoretinoin, has a half life of several days. Seven defect outcomes and one stillbirth have been reported with another congener, etretinate (ETR), used for psoriasis. Three of these had meningomyeloceles. Half life of several months makes levels cumulative. Only one additional defect, which may have occurred by chance, is reported with use stopped before conception (4 months). Other discontinuations 1 to 6 months before conception had 11 normal outcomes and two spontaneous abortions. ITR and ETR dose ranged from 0.5 to 1.5 mg/kg. Normal outcomes are reported both with ITR and ETR, but some of these appear not to have been exposed during the critical period. Less striking defects, abortions, and normal outcomes are less well reported. Because vitamin A analogs are therapeutically important and unplanned outcome not always avoidable, further animal research is needed for better risk/benefits. Megadose vitamin A (retinol) use is widespread, but experience poorly observed. Eighteen suspicious birth defect outcomes have been reported from pregnancies with high dose exposure. Twelve had findings similar to those seen in animals and in human retinoid syndromes, e.g., CNS, CV, microtia, and clefts. Epidemiological controls are lacking to establish human teratogenicity, but based on animal studies and experience with ITR and ETR, avoiding long term megadose Vitamin A use in fertile women is warranted.