E. Haydn Walters

Influence of Pulmonary Capillary Wedge Pressure on Central Apnea in Heart Failure

BACKGROUND Recent studies suggest that acute pulmonary congestion induces hyperventilation and that hyperventilation-related hypocapnia leads to ventilatory control instability and central sleep apnea. Whether chronic pulmonary congestion due to congestive heart failure (CHF) is associated with central apnea is unknown. We hypothesized that CHF patients with central apnea would have greater pulmonary capillary wedge pressure (PCWP) than patients without central apnea and that PCWP would correlate with central apnea severity. METHODS AND RESULTS Seventy-five stable CHF patients underwent right heart catheterization and, on the basis of overnight sleep studies, were divided into central apnea (n=33), obstructive apnea (n=20), or nonapnea groups (apnea-hypopnea index [AHI] <5 events per hour). Mean PCWP was significantly greater in the central than in the obstructive and nonapnea groups (mean+/-SEM [range]: 22. 8+/-1.2 [11 to 38] versus 12.3+/-1.2 [4 to 21] versus 11.5+/-1.5 [3 to 28] mm Hg, respectively; P<0.001). Within the central apnea group, PCWP correlated with the frequency and severity of central apnea (AHI: r=0.47, P=0.006) and degree of hypocapnia (PaCO2: r=-0.42, P=0. 017). Intensive medical therapy in 7 patients with initially high PCWP and central apneas reduced both PCWP (29.0+/-2.6 [20 to 38] to 22.0+/-1.8 [17 to 27] mm Hg; P<0.001) and central apnea frequency (AHI) (38.5+/-7.7 [7 to 62] to 18.5+/-5.3 [1 to 31] events per hour; P=0.005). CONCLUSIONS PCWP is elevated in CHF patients with central apneas compared with those with obstructive apnea or without apnea. Moreover, a highly significant relationship exists between PCWP, hypocapnia, and central apnea frequency and severity.

Prevalence of food allergies in young adults and their relationship to asthma, nasal allergies, and eczema

BACKGROUND The true prevalence of food allergy in adults is generally thought to be uncommon. It is unknown whether there are any relationships between food allergy and atopic diseases. OBJECTIVE To determine the prevalence of probable immunoglobulin (Ig)E-mediated food allergy to peanut, shrimp, cows milk, wheat, and egg as defined by a positive skin prick test result and relevant clinical history to the same food, and to explore the relationship with atopic diseases. METHODS Cross-sectional epidemiologic study. One thousand one hundred forty-one randomly selected young adults (aged 20 to 45 years) underwent skin prick testing to five common food allergens (cows milk, peanut, egg white, shrimp, and wheat), completed a detailed questionnaire, including validated items on respiratory symptoms, history of asthma and other allergic conditions, as well as undergoing lung function testing. RESULTS Just over one percent (1.3%, n = 15) had probable IgE-mediated food allergy. The prevalence of probable IgE food allergy was: <0.27% for wheat, 0.09% (95% confidence interval = 0.0 to 0.49%) each for cows milk and egg, 0.53% (0.21 to 1.09%) for shrimp, and 0.61% (0.25 to 1.26%) for peanut. Those with probable IgE peanut and shrimp allergy were significantly more likely to have current asthma and doctor-diagnosed asthma. Wheeze and history of eczema were also associated with peanut allergy, whereas nasal allergies were associated with shrimp allergy. CONCLUSIONS The prevalence of probable IgE-mediated food reactions is rare in young adults. Some positive associations between probable IgE-mediated food allergy and allergic diseases were found, but larger study numbers are required to confirm these results.

Childhood eczema and rhinitis predict atopic but not nonatopic adult asthma: A prospective cohort study over 4 decades

BACKGROUND The evidence on whether the atopic march observed in childhood (ie, the progression from eczema to allergic rhinitis and asthma) extends to adulthood is sparse, and there is no evidence on whether the progression leads to a specific phenotype of asthma. OBJECTIVE We sought to assess whether childhood eczema and rhinitis are risk factors for specific phenotypes of adult asthma. METHODS Participants of the Tasmanian Longitudinal Health Study recruited in 1968 (age range, 6.0-7.0 years) were followed up at age 44 years. The risk of current atopic or nonatopic asthma in middle age characterized by sensitization to aeroallergens given childhood eczema, rhinitis, or both was calculated by using multinomial logistic regression. RESULTS No association was found between childhood eczema or rhinitis and nonatopic adult asthma. In contrast, childhood eczema and rhinitis in combination predicted both new-onset atopic asthma by middle age (adjusted multinomial odds ratio [aMOR], 6.3; 95% CI, 1.7-23.2) and the persistence of childhood asthma to adult atopic asthma (aMOR, 11.7; 95% CI, 3.6-37.9). Participants with childhood eczema alone were at increased risk of new-onset atopic asthma (aMOR, 4.1; 95% CI, 1.9-8.8), whereas rhinitis alone predicted the persistence of childhood asthma to atopic asthma (aMOR, 2.7; 95% CI, 1.3-5.6). Of all asthma, 29.7% of persistent atopic asthma and 18.1% of new-onset atopic asthma could be attributed to having childhood eczema and rhinitis. CONCLUSION Childhood eczema and rhinitis are strongly associated with the incidence and persistence of adult atopic asthma.

Childhood eczema and asthma incidence and persistence: A cohort study from childhood to middle age

BACKGROUND The association between eczema and asthma is well documented, but the temporal sequence of this association has not been closely examined. OBJECTIVES To examine the association between childhood eczema and asthma incidence from preadolescence to middle age, and between childhood eczema and asthma persisting to middle age. A further aim was to examine any effect modification by nonallergic childhood exposures on the association between childhood eczema and both childhood asthma and later life incident asthma. METHODS Data were gathered from the 1968, 1974, and 2004 surveys of the Tasmanian Longitudinal Health Study. Multivariable logistic regression examined the association between childhood eczema and childhood asthma. Cox regression examined the association between childhood eczema and asthma incidence in preadolescence, adolescence, and adult life. Binomial regression examined the association between childhood eczema and childhood asthma persisting to age 44 years. RESULTS Childhood eczema was significantly associated with childhood asthma and with incident asthma in preadolescence (hazard ratio [HR], 1.70; 95% CI, 1.05-2.75), adolescence (HR, 2.14; 95% CI, 1.33-3.46), and adult life (HR, 1.63; 95% CI, 1.28-2.09). Although childhood eczema was significantly associated with asthma persisting from childhood to middle age (relative risk, 1.54; 95% CI, 1.17-2.04), this association was no longer evident when adjusted for allergic rhinitis. CONCLUSION Childhood eczema increased the likelihood of childhood asthma, of new-onset asthma in later life and of asthma persisting into middle age.

Factors influencing asthma remission: a longitudinal study from childhood to middle age

Objective To examine asthma remission from childhood to middle age. Methods This was a population-based cohort study. In 1968 the Tasmanian Longitudinal Health Study enrolled 8583 7-year-old Tasmanian schoolchildren who were re-surveyed in 2004. Those reporting ever having asthma when last surveyed completed another questionnaire in 2007 ascertaining age at last asthma attack and asthma medication use. The main outcome measure was asthma remission, defined as no asthma attack for 2 years and no current asthma medication use, or no self-reported asthma in adult life but with parent-reported childhood asthma. Results Of 5729 respondents to the 2004 survey, 1238 self-reported asthma. A further 573 denied asthma, but had parent-reported childhood asthma, giving a study sample of 1811. Asthma had remitted in 1177 (65.0%) of whom 649 (55.1%) were male. Childhood (OR 0.38, 95% CI 0.25 to 0.58) and later-onset allergic rhinitis (0.42, 0.29 to 0.63), childhood (0.66, 0.47 to 0.94) and later-onset eczema (0.66, 0.47 to 0.92), maternal asthma (0.66, 0.47 to 0.92) and childhood chronic bronchitis (0.56, 0.41 to 0.76) were negatively associated with remission. There was weaker evidence for a negative association between passive smoking (0.75, 0.54 to 1.04) and lower socio-economic status (p-trend 0.09) and remission. Childhood-onset asthma (3.76, 2.58 to 5.49) was more likely to remit than adult-onset asthma. Adult smoking was positively associated with remission in childhood-onset asthma (1.49, 1.06 to 2.09). Sex did not influence remission. Conclusion While inherited factors cannot be changed, the effect of allergic rhinitis or eczema on asthma remission might be altered by early, aggressive treatment. Every effort should be made to lessen passive exposure to tobacco smoke.

Addition of inhaled corticosteroids to systemic immunosuppression after lung transplantation: a double-blind, placebo-controlled trial.

Background. It is postulated that bronchiolitis obliterans syndrome (BOS) is preceded by airway inflammation that has been described even in stable lung transplant recipients. Airway inflammation is known to be suppressed by inhaled steroids in other chronic inflammatory lung diseases, e.g., asthma and chronic obstructive pulmonary disease. BOS is the major cause of morbidity and mortality after lung transplantation. Objective. To examine the effect of inhaled corticosteroids on the development of BOS in lung transplant recipients. Methods. Thirty patients were recruited and randomized in a double-blind fashion to receive either 750 &mgr;g of fluticasone propionate (FP) or an identical-appearing placebo twice daily for 3 months; 20 of this group continued until 2 years posttransplantation. Detailed spirometry was performed regularly throughout the study. Results. In the short-term study no differences were found in any examined parameters. In the long-term component of the study no differences were found in the development of neither BOS nor survival. There were minor differences in bronchoalveolar lavage (BAL) lymphocyte percentages. Conclusions. FP is ineffective for the prevention of BOS after lung transplantation despite the airway inflammation that characterizes this condition. Inadequate local delivery, timing of the therapy relative to transplantation and inherent steroid resistance of this condition may explain the negative finding of this study.

Risk factors for asthma among young adults in Melbourne, Australia

Abstract Asthma is more prevalent in Australia than in Europe or North America. As part of the European Community Respiratory Health Survey (ECRHS), we investigated exposure to risk factors for asthma among young adults in Melbourne. During this study, 553 randomly selected and 204 symptomatic participants aged between 20 and 44 years completed a detailed respiratory questionnaire, of whom 675 underwent measurement of bronchial hyperreactivity (BHR) by methacholine challenge and 745 had skin prick tests for atopy. Current asthma, defined as BHR and wheeze in the preceding 12 months, was present in 25.5% of those tested. A family history of asthma was a risk factor for current asthma (maternal asthma odds ratio [OR] 2.4, paternal asthma OR 2.1). Current smokers were 1.7 times more likely to have current asthma. A serious respiratory infection before 5 years of age increased the risk of current asthma 2.3‐fold. Atopy on skin testing was also strongly associated with current asthma (OR 5.9). The greatest risks were associated with positive skin tests to Cladosporium, house dust mite, cat and rye grass pollen. We conclude that female gender, maternal asthma, smoking, hayfever, early respiratory infection, occupational exposure and atopy are important risk factors for asthma in young adults.

Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study

BackgroundLittle is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD). We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.MethodsTo determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.ResultsThickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects. Rbm fragmentation correlated with smoking history in COPD but not with age. There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05). The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004). In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).ConclusionsAirway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.

Written action plans in chronic obstructive pulmonary disease increase appropriate treatment for acute exacerbations

Objective and background:  COPD is a progressive disorder characterized by periodic exacerbations. While comprehensive self‐management programmes decrease health‐care resource utilization, the essential components are unclear. We performed a study of written action plans in the management of COPD.

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

AbstractThe β2-adrenergic receptor (β2AR) is a transmembrane protein expressed by airway smooth muscle cells. In vitro studies have shown that polymorphisms at amino acid positions 16 and 27 alter receptor function. The aim of this study was to examine the associations between the β2AR polymorphisms and risks of asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in a sample of adults. Participants were part of a cross-sectional population-based study of risk factors for respiratory disease. A total of 1,090 Caucasian participants completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of gas transfer. Genotyping for β2AR polymorphisms at positions 16 and 27 was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Haplotype frequencies for the two polymorphisms were estimated using the E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR 5.13; 95% CI 1.40,18.8), asthma (2.44; 1.12,5.31) and symptoms of wheeze (1.84; 1.02,3.35). The Gln27 homozygotes had an increased risk of asthma (2.08; 1.05,4.13) and bronchial hyperreactivity (BHR) (1.92; 1.07,3.46). The Arg16/Gln27 haplotype was associated with asthma (1.63; 1.12,2.38) and COPD (2.91; 1.42,5.94). The Arg16/Gln27 β2AR haplotype is important in COPD, asthma and BHR, and may be associated with more severe respiratory symptoms in middle-aged and older adults.