Marcy F. Petrini

Mechanical ventilation in patients with acute severe asthma

Abstract purpose: Acute respiratory failure necessitating intubation and mechanical ventilation in patients with acute severer asthma is relatively uncommon, and there are few data available regarding positive pressure ventilation in critically ill patients with asthma. We therefore decided to evaluate our experience with the use of mechanical ventilation for acute asthma and to critically review previous reports on this subject. patietns and methods: A retrospective analysis of all medical records of patients who required mechanical ventilation for acute severe asthma was performed for the period of 1980 to 1988. Various clinical parameters were reviewed and examined via Fishers exact test for association with survival. results: Twenty-seven patients who underwent ventilation for a total of 32 episodes of mechanical ventilation comprised our study group. The overall mortality was 22%. A total of 76 complications were documented, including six episodes of baro-trauma. The mean duration of artificial ventilation was 114 hours for nonsurvivors and 77 hours for survivors (p conclusion: Although there appears to be a trend toward increased survival after mechanical ventilation for acute asthma, ventilation of critically ill asthmatic patients continues to be a potentially perilous ventures associated with significant morbidity and mortality.

Calcium Mobilization and Muscle Contraction Induced by Acetylcholine in Swine Trachealis.

The roles of Ca(2+) mobilization in development of tension induced by acetylcholine (ACh, 0.1-100 &mgr;M) in swine tracheal smooth muscle strips were studied. Under control conditions, ACh induced a transient increase in free cytosolic calcium concentration ([Ca(2+)](i)) that declined to a steady-state level. The peak increase in [Ca(2+)](i) correlated with the magnitude of tension at each [ACh] after a single exposure to ACh, while the steady-state [Ca(2+)](i) did not. Removal of extracellular Ca(2+) had little effect on peak [Ca(2+)](i) but greatly reduced steady-state increases in [Ca(2+)](i) and tension. Verapamil inhibited steady-state [Ca(2+)](i) only at [ACh] <1 &mgr;M. After depletion of internal Ca(2+) stores by 10 min exposure to ACh in Ca(2+)-free solution and then washout of ACh for 5 min in Ca(2+)-free solution, simultaneous re-exposure to ACh in the presence of 2.5 mM Ca(2+) increased [Ca(2+)](i) to the control steady-state level without overshoot. The tension attained was the same as control for each [ACh] used. Continuous exposure to successively increasing [ACh] (0.1-100 &mgr;M) also reduced the overshoot of [Ca(2+)](i) at 10 and 100 &mgr;M ACh, yet tension reached control levels at each [ACh] used. We conclude that the steady-state increase in [Ca(2+)](i) is necessary for tension maintenance and is dependent on Ca(2+) influx through voltage-gated calcium channels at 0.1 &mgr;M ACh and through a verapamil-intensitive pathway at 10 and 100 &mgr;M. The initial transient increase in calcium arises from intracellular stores and is correlated with the magnitude of tension only in muscles that have completely recovered from previous exposure to agonists. Copyright 2001 S. Karger AG, Basel

Leptin is inversely associated with lung function in African Americans, independent of adiposity: the Jackson Heart Study.

Leptin, a 16‐kDa protein, has proinflammatory properties and has been linked to respiratory physiological responses in majority white populations. Little is known, however, about the relationship of leptin with lung function in nonwhites. Cross‐sectional associations of circulating serum leptin concentrations with forced expiratory volume in 1 s (FEV1), FEV in 6 s (FEV6), and vital capacity (FVC), assessed by spirometry, were examined in 4,679 African‐American men and women participants (54.3 ± 12.4 years; 62.7% women) in the Jackson Heart Study (JHS). The independent association of leptin was examined in relation to FEV1, FEV6, and FVC% predicted after adjustment for age, education, smoking status, pack‐years of cigarette smoking, respiratory medication use, and menopausal status in women; additional adjustment included total body weight, waist circumference, and BMI. Serum leptin was inversely related to FEV1, FEV6, and FVC% predicted values in men. A dose‐response relationship was observed with men in the highest leptin quartile having a significantly lower lung function compared to men in the lower leptin quartile. BMI significantly modified this relationship in women: leptin was most consistently associated with lung function in obese women, less consistent in overweight women, and absent in normal‐weight women. Serum leptin concentration was strongly, inversely, and independently associated with lung function in African Americans, especially African‐American men and obese women.

Pericardial Fat Is Associated With Impaired Lung Function and a Restrictive Lung Pattern in Adults: The Jackson Heart Study

BACKGROUND Impaired lung function has been linked to obesity and systemic inflammation. Pericardial fat has been shown to be associated with anomalies in cardiac structure, function, and atherosclerosis. We hypothesized that pericardial fat may have a similar role in the impairment of lung function. METHODS Cross-sectional associations of pericardial fat volumes, quantified by multidetector CT scan, with FEV(1) and FVC assessed by spirometry, were investigated in 1,293 participants (54.5 ± 10.8 years; 66.4% women) in the Jackson Heart Study. We also examined whether these associations were independent of visceral adipose tissue (VAT). RESULTS Pericardial fat was associated with impaired lung function after multivariable adjustment, but these associations generally did not remain after adjustment for VAT. An exception was the FEV(1)/FVC ratio. Higher pericardial fat volumes were associated with higher odds of a restrictive lung pattern and lower odds of airway obstruction. Participants in the highest quartile had the highest odds of a restrictive lung pattern (OR, 1.85; 95% CI, 1.22-2.79, compared with quartile 1), even after adjustment for VAT. The odds of obstruction decreased across increasing quartiles of pericardial fat. These relationships were generally graded, suggesting dose-response trends. CONCLUSIONS Pericardial fat is generally associated with lower lung function and independently associated with a restrictive lung pattern in middle-aged and elderly adults. Further research is needed to fully understand the mechanisms through which pericardial fat contributes to pulmonary anomalies.

Asthma and Asthma Severity among African American Adults in the Jackson Heart Study

The aims of this study were to investigate the baseline prevalence of and risk factors associated with asthma, classify asthma severity, and describe medication use in a population-based sample of African American men and women 21 to 84 years of age from the Jackson Heart Study (JHS). Participants provided responses to respiratory and medical history questions and a medication inventory and underwent spirometry and other clinical examinations. These data were used to examine the extent to which novel and traditional risk factors were associated with asthma. Of the 4,098 participants included in this analysis, 9.4% reported lifetime asthma (5.7% current, 3.7% former), and current asthma was higher in women (6.8%) than in men (3.8%). An additional 9.8% reported an attack of wheeze with shortness of breath or non-doctor confirmed asthma (i.e., “probable” asthma). The mean forced expiratory volume in 1 second (FEV1)% predicted was lower in those reporting current asthma (women: 83.7 ± 18.0; men: 75.2 ± 16.8) compared to those not reporting asthma (women: 95.6 ± 16.7; men: 91.7 ± 16.0). Current and probable asthma was associated with lower serum cortisol levels and hypertension medication use, along with traditional risk factors (i.e., lower socio-economic status, higher global stress scores, obesity, and fair to poor perceived general health). Severe asthma was low among participants reporting current (9.8%), former (3.3%), and probable (4.9%) asthma. Asthma medication use was reported by nearly 60% of the participants reporting current asthma. Asthma in African American adults is associated with decreased serum cortisol, hypertension medication use, and considerable lung function impairment compared to those who did not report asthma. The prevalence of asthma in the JHS is lower than state and national estimates, although the estimates are not directly comparable. Furthermore, asthma is drastically underdiagnosed in this population.

Replication and fine mapping of asthma-associated loci in individuals of African ancestry

Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.

Effect of Smoking on Spirometry of African American and White Subjects

BACKGROUND Smoking is the single most important risk factor for COPD, yet there is still disagreement about the differences in the effect of smoking between white and African-American people. We hypothesized that the results of spirometry between smokers of the two races are equivalent if reference equations and lower limits of normal appropriate for each race are used. METHODS We retrospectively analyzed all spirometry results in smokers over a 1-year period from the G.V. (Sonny) Montgomery VA Medical Center and excluded those that did not meet American Thoracic Society standards, or those from patients with additional medical problems. The remaining patients were classified by race and then matched for age and smoking history; 108 patients in each group were included, which met the power analysis goal of 98. The two groups were similar in age (57.5 years vs 57.0 years), smoking history (46.1 pack-years vs 46.0 pack-years), and body mass index (27.0 kg/m(2) vs 28.3 kg/m(2)) for African Americans and whites, respectively. Data were analyzed using the unpaired t test, and p values were adjusted for multiple comparisons using the Bonferroni factor. RESULTS There were statistically significant differences between African American and white smokers in FVC (3.67 +/- 0.07 L vs 4.26 +/- 0.08 L, p = 0.001) and FEV(1) (2.33 +/- 0.07 L vs 2.72 +/- 0.08 L, p = 0.002), as expected from the normal populations; however, there were no differences in FVC as percentage of predicted (89.1 +/- 1.3% vs 86.7 +/- 1.5%, p = 0.71) and FEV(1) as percentage of predicted (71.9 +/- 2.1% vs 72.2 +/- 1.8%, p = 1.00) when the reference equations appropriate for race were used (third National Health and Nutrition Examination Survey). There were also no differences between the number of subject with abnormal FEV(1)/FVC results (56 African Americans vs 58 whites, p = 1.00) when the appropriate lower limits of normal were used. CONCLUSIONS There are no differences in spirometry findings between African Americans and whites when abnormality is defined appropriately using reference equations and lower limits of normal for each race. By using either percentage cutoffs for abnormality, or by adjusting for African-American equations only appropriate for whites, we were able to mimic with our data conflicting results in the literature.

Pulmonary tissue volume and blood flow as functions of body surface area and age

AbstractWe measured pulmonary tissue volume (Vt) and capillary blood flow

Distribution of ventilation and perfusion: A teaching model

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