Alfa 1 antitrypsin and protease levels in Puerto Rican asthmatics: a pilot study.

A cross-sectional pilot study was conducted on a population of 119 asthmatics who had been recruited from the Emergency Room Department of a major hospital in Ponce, Puerto Rico. The purpose of the study was to determine the frequency of the MM, MS, and SS a-i-antiprotease variants. Also, we analyzed the serum levels of the alpha-1-antiprotease inhibitor, quantified the levels of serine proteases in homes of the asthmatic volunteers, and determined whether environmental levels of proteases, regardless of their sources, had any association with either asthma symptoms or alpha-1-antiprotease inhibitor phenotypes. Our results do not support the role of the alpha-1-antiprotease as a risk factor for asthma in the study population as previously reported. Patients who had visited the ED due to asthma on 3 or more occasions had significantly higher trypsin levels than those who had done so 2 or fewer times. Of those asthmatic patients who had daily symptoms, 40% had been exposed to high levels of elastase, and 33.3% to trypsin. Similarly, 52.9% of the patients with 2 or more hospitalizations a year had been exposed to high elastase levels, and 40.5% of asthma patients who had nocturnal asthma more than 3 times a week had been exposed to high levels of elastase.

Age, gender and seasonal patterns of asthma in emergency departments of southern Puerto Rico.

We report findings derived from 55,547 emergency department records of asthmatic patients in the city of Ponce, Puerto Rico over a period of six years. The analysis of the data revealed that mean age of the asthmatic cases were 18.7 +/- 17.8 years, with 45% percent of the patients in the 1-9 years age range, and proportionally decreasing with age. In children 1-9 years the percent of males was 1.5 times that of females, and in 10-19 year-old group, admissions to the emergency room for males and females was identical, and between 20-69 years of age, the female ratio ranged from 1.5-2.12. The data also demonstrated that there is a seasonal variation in the asthma attacks reaching its peak in December, and the lowest in June. In conclusion, in the city of Ponce, Puerto Rico, emergency department usage due to asthma attacks show a seasonal variation, and males are more affected by asthma at younger ages while females are more affected at older ages. These findings strongly suggest that emergency department usage due to asthma attacks is highly common and represents an important place where specialized health care delivery is needed. With the implementation of dedicated asthma centers, specialized health care delivery can be easily accomplished. In addition, our data supports the that asthma should be declared a public health problem and a reportable disease.

Effect of rare variants in ADRB2 on risk of severe exacerbations and symptom control during longacting ß agonist treatment in a multiethnic asthma population: a genetic study.

BACKGROUND: Severe adverse life-threatening events associated with longacting ß agonist (LABA) use have caused the US Food and Drug Administration (FDA) to review the safety of these drugs, resulting in a boxed warning and a mandatory safety study in 46 800 patients with asthma. Identification of an at-risk, susceptible subpopulation on the basis of predictive biomarkers is crucial for understanding LABA safety. The ß2-adrenergic receptor gene (ADRB2) contains a common, non-synonymous single nucleotide polymorphism, Gly16Arg, that is unlikely to account for the rare, life-threatening events seen with LABA use. We hypothesise that rare ADRB2 variants modulate therapeutic responses to LABA therapy and contribute to rare, severe adverse events. METHODS: In this genetic study, ADRB2 was sequenced in 197 African American, 191 non-Hispanic white, and 73 Puerto Rican patients. Sequencing identified six rare variants, which were genotyped in 1165 patients with asthma. The primary hypothesis was that severe asthma exacerbations requiring hospital admission were associated with rare ADRB2 variants in patients receiving LABA therapy. This outcome was assessed overall and by ethnic group. Replication was done in 659 non-Hispanic white patients with asthma. FINDINGS: Patients receiving LABA with a rare ADRB2 variant had increased asthma-related hospital admissions (15 [44%] of 34 patients with rare variant vs 121 [22%] of 553 patients with common ADRB2 alleles admitted to hospital in past 12 months; meta-analysis for all ethnic groups, p=0·0003). Specifically, increases in hospital admission rates were recorded in LABA-treated non-Hispanic white patients with the rare Ile 164 allele compared with non-Hispanic white patients with the common allele (odds ratio [OR] 4·48, 95% CI 1·40-13·96, p=0·01) and African American patients with a 25 bp promoter polynucleotide insertion, -376ins, compared with African American patients with the common allele (OR 13·43, 95% CI 2·02-265·42, p=0·006). The subset of non-Hispanic white and African American patients receiving LABAs with these rare variants had increased exacerbations requiring urgent outpatient health-care visits (non-Hispanic white patients with or without the rare Ile 164 allele, 2·6 [SD 3·5] vs 1·1 [2·1] visits, p<0·0001; and African American patients with or without the rare insertion, 3·7 [4·6] vs 2·4 [3·4] visits, p=0·01), and more frequently were treated with chronic systemic corticosteroids (OR 4·25, 95% CI 1·38-14·41, p=0·01, and 12·83, 1·96-251·93, p=0·006). Non-Hispanic white patients from the primary and replication cohorts with the rare Ile 164 allele were more than twice as likely as Thr 164 homozygotes to have uncontrolled, persistent symptoms during LABA treatment (p=0·008-0·04). INTERPRETATION: The rare ADRB2 variants Ile164 and -376ins are associated with adverse events during LABA therapy and should be evaluated in large clinical trials including the current FDA-mandated safety study. FUNDING: US National Institutes of Health.

Measuring asthma disparities in Hispanics: adherence to the national guidelines for asthma treatment in emergency departments in Puerto Rico.

BACKGROUND: Puerto Rico has the highest prevalence of asthma in the United States. Currently, there are no data on actual care given to asthmatic patients. OBJECTIVE: To determine the prevalence of documented adherence to the 1997 National Asthma Education Prevention Program guidelines regarding care given in emergency departments (EDs) in Ponce, Puerto Rico. METHODS: A case series was conducted using 6,002 ED records with a physician-based diagnosis of asthma for 1999 through 2001. RESULTS: A history of asthma attack was documented in 82.0% of the cases and in all age groups. In-home beta-agonist use was recorded in only 5.7% of the medical records. Documentation of previous admissions to the ED and the intensive care unit were found in 3.5% and 0.33% of the records, respectively. Nocturnal symptoms before the ED visit were found in only 6.4% of the records, and asthma treatment at home was found in 39.9%. Accessory muscle retraction was documented in 99.1% of the cases, and oxygen saturation was found in 23.2%. Treatment with nebulized beta-agonist was found in 72.1% of the records, and intravenous or oral corticosteroid use was found in 84.1%. Follow-up appointments were detected in 64.8% of the cases, and referrals to specialists were given in only 5.3%. Rate ratios between our data and those of other researchers indicate that there are geographical differences in compliance with the guidelines. CONCLUSION: Of the variables tested, only one had acceptable levels of compliance, as evidenced in the patient's records, indicating that there are alarming differences in ED evaluation and treatment compared with the 1997 National Asthma Education Prevention Program guidelines.

Exposure levels of asthmatic children to allergens, endotoxins, and serine proteases in a tropical environment.

A cross-sectional study was conducted in Bayamón, Puerto Rico, to identify and quantify indoor allergens, serine proteases, and bacterial endotoxin present in homes of asthmatic children. A total of 126 dust samples from houses were obtained from the entire mattress and bedside floor. Most of the patients had detectable levels of mite, cockroach, cat, and dog allergens. Mold allergens were found only in bedside floor dust samples. Mouse allergens were not detected. Forty-two percent, 36.5%, and 1.8% of the patients demonstrated exposures to sensitizing levels of mite, Bla g 1 and cat allergens, respectively. The percentage of patients exposed to high levels of allergens capable of triggering asthma symptoms was 33.3% and 26.4% for mite and Bla g 1 allergens. Only dog allergen, bacterial endotoxin, elastase, and trypsin were associated with asthma symptoms. Eighty-nine percent of the asthmatic children were exposed to endotoxin concentrations greater than 100 EU/mg dust, and more than half of the patients were exposed to high levels of serine proteases. Our study indicates that indoor concentrations of allergens traditionally associated with asthma symptoms and severity may not be applicable in tropical environments and highly ventilated households. In fact, in the study population, endotoxins, dog allergen, and serine proteases may play a dominant role in the induction of asthma symptoms.

Age, gender and seasonal patterns of asthma in emergency departments of southern Puerto Rico

We report findings derived from 55,547 emergency department records of asthmatic patients in the city of Ponce, Puerto Rico over a period of six years. The analysis of the data revealed that mean age of the asthmatic cases were 18.7 +/- 17.8 years, with 45 percent of the patients in the 1-9 years age range, and proportionally decreasing with age. In children 1-9 years the percent of males was 1.5 times that of females, and in 10-19 year-old group, admissions to the emergency room for males and females was identical, and between 20-69 years of age, the female ratio ranged from 1.5-2.12. The data also demonstrated that there is a seasonal variation in the asthma attacks reaching its peak in December, and the lowest in June. In conclusion, in the city of Ponce, Puerto Rico, emergency department usage due to asthma attacks show a seasonal variation, and males are more affected by asthma at younger ages while females are more affected at older ages. These findings strongly suggest that emergency department usage due to asthma attacks is highly common and represents an important place where specialized health care delivery is needed. With the implementation of dedicated asthma centers, specialized health care delivery can be easily accomplished. In addition, our data supports the that asthma should be declared a public health problem and a reportable disease.

Prevalence of skin reactions to aeroallergens in asthmatics of Puerto Rico

In Puerto Rico, although a high prevalence of asthma has been reported, the sensitization rates to aeroallergens in these patients is unknown. The purpose of this study using a case control design, was to determine and compare the rates of sensitization to common aeroallergens in an asthmatic population of 576 asthmatics and 144 healthy controls. A skin prick test was conducted using standardized extracts of Dermatophagoides farinae (Df) and D. pteronyssinus (Dp), house dust (HD), cat hair and epithelium (CT), dog hair and dander (DG), grass pollen mix (PG), tree pollen mix (PT), weed pollen mix (PW), Aspergillus mix (AM), mold mixes A (MA) and B (MB), Periplaneta americana (PA) and Alternaria-Hormodendrum mix (AH). In addition, an extract from the domestic mite Blomia tropicalis (Bt) was also used. A wheal > or = 3 mm2 was considered a positive reaction. In addition, a standardized questionnaire was administered and a preliminary domestic mite identification survey was conducted. The analysis of the data showed that 85.8 of the asthmatics had at least one positive reaction and 61.6 of them had positive skin reactions to atleast one mite species. Asthmatics reacted to domestic mites 6.19 times more than the control group (p < 0.0001) and was the largest significant difference found in this study for any allergen tested. Preliminary identification of the acarologic fauna in southern Puerto Rico demonstrated that Blomia tropicalis, Dermatophagoides pteronyssinus, D. farinae and E.maynei are the dominant domestic mite species found in homes of asthmatic individuals. These results demonstrate that domestic mites are a very important source of sensitizing aeroallergens for asthmatic patients in Puerto Rico. Based upon the mite survey, Blomia tropicalis plays an important role in allergic sensitization, in addition to Dermatophagoides pteronyssinus and D. farinae. The skin prevalence to pollens and to molds may not reflect the true prevalence of sensitization to these allergens. Pollen identification and counts, and a survey of microflora of Puerto Rico are needed in order to identify and validate important allergens that eventually could be incorporated into a more appropria).te panel for testing sensitization in susceptible individuals