Severe airway stenosis associated with Crohn's disease: Case report

Background

Although it is recognised that smoking is a major risk factor for subjects with chronic obstructive pulmonary disease and is associated with respiratory symptoms, there is less agreement concerning the relationship between asthma and smoking. This study aims to examine the relationship between cigarette smoking and asthma prevalence.

Method

Data were used from two postal questionnaire surveys (1999 and 2001) in two general practice populations, using a respiratory questionnaire based on the ECRHQ and a generic quality of life questionnaire (EQ-5D). Only subjects less than 45 years old were included in the survey. An empirical definition of likely asthma was used based on respiratory questionnaire responses. Smoking was examined according to three categories, current smoker, ex smoker and never smoker.

Results

Almost 3500 subjects were included in the analyses. Current smokers had a higher prevalence of likely asthma compared to never smokers, odds ratio (OR) 1.59 (95% confidence interval (CI) 1.24 to 2.04). and also compared to ex smokers OR 1.79 (CI 1.25 to 2.56), but there was no difference between ex smokers and never smokers (OR 1.00 (0.75–1.35)). Current smoking was also positively associated with all symptoms but not with a history of hayfever/eczema.

Conclusion

Although the positive association found between current smoking and obstructive airways disease is likely to be due to the effect of cigarettes on asthma, it could reflect an association with early COPD (GOLD stages 0 or 1). Smoking cessation has a beneficial effect on the prevalence of respiratory symptoms and is therefore of paramount importance among these young adults.     

Safety and efficacy of fluticasone/formoterol combination therapy in adolescent and adult patients with mild-to-moderate asthma: a randomised controlled trial

Background

Early wheezing and asthma are relevant health problems in the tropics. Mite sensitization is an important risk factor, but the roles of others, inherent in poverty, are unknown. We designed a birth-cohort study in Cartagena (Colombia) to investigate genetic and environmental risk factors for asthma and atopy, considering as particular features perennial exposure to mites, parasite infections and poor living conditions.

Methods

Pregnant women representative of the low-income suburbs of the city were randomly screened for eligibility at delivery; 326 mother-infant pairs were included at baseline and biological samples were collected from birth to 24 months for immunological testing, molecular genetics and gene expression analysis. Pre and post-natal information was collected using questionnaires.

Results

94% of families were from the poorest communes of the city, 40% lacked sewage and 11% tap-water. Intestinal parasites were found as early as 3 months; by the second year, 37.9% of children have had parasites and 5.22% detectable eggs of Ascaris lumbricoides in stools (Median 3458 epg, IQR 975-9256). The prevalence of "wheezing ever" was 17.5% at 6 months, 31.1% at 12 months and 38.3% at 24 months; and recurrent wheezing (3 or more episodes) 7.1% at 12 months and 14.2% at 24 months. Maternal rhinitis [aOR 3.03 (95%CI 1.60-5.74), p = 0.001] and male gender [aOR 2.09 (95%CI 1.09 - 4.01), p = 0.026], increased risk for wheezing at 6 months. At 24 months, maternal asthma was the main predisposing factor for wheezing [aOR 3.65 (95%CI 1.23-10.8), p = 0.01]. Clinical symptoms of milk/egg allergy or other food-induced allergies were scarce (1.8%) and no case of atopic eczema was observed.

Conclusions

Wheezing is the most frequent phenotype during the first 24 months of life and is strongly associated with maternal asthma. At 24 months, the natural history of allergic symptoms is different to the "atopic march" described in some industrialized countries. This cohort is representative of socially deprived urban areas of underdeveloped tropical countries. The collection of biological samples, data on exposure and defined phenotypes, will contribute to understand the gene/environment interactions leading to allergy inception and evolution.     

Pulmonary function,exhaled nitric oxide and symptoms in asthma patients with obesity: a cross-sectional study

Background

Obesity is a risk factor for the development of asthma. In patients with obesity the diagnosis of asthma is often based on symptoms, but without objective measurements. Nevertheless, obesity-associated asthma is recognized as a distinct asthma phenotype. Therefore, this study explores lung function and symptoms in asthma patients with and without obesity.

Methods

The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort study with 6671 participants (aged 45–65 years) of whom 472 had asthma. Of this latter group, linear regression analysis was used to examine differences in lung function and symptoms between asthma patients with (n?=?248) and without obesity (n?=?224), and between asthma patients with and without increased Fe_NO. Analyses were adjusted for confounders.

Results

Asthma patients with obesity had lower predicted FEV₁ and FVC values than patients without obesity [adjusted mean difference (MD) -3.3% predicted, 95% CI -6.5, ?0.2; adjusted MD ?5.0% predicted, 95% CI -7.8, ?2.1]. The prevalence of symptoms was higher in patients with obesity. Asthma patients with obesity and with increased Fe_NO had lower FEV₁ and FEV₁/FVC values compared with those with low Fe_NO (adjusted MD ?6.9% predicted, 95% CI -11.7, ?2.0; ?2.4%, 95% CI -4.6, ?0.2).

Conclusion

Asthma patients with obesity had lower FEV₁ and FVC values than patients without obesity. This suggests that patients with obesity have restrictive lung function changes, rather than obstructive changes. Asthma patients with obesity and increased Fe_NO showed more obstructive changes. Fe_NO might help to identify patients with eosinophilic inflammation-driven asthma, whereas patients with low Fe_NO might have an obesity-associated asthma phenotype in which symptoms are partly caused by the obesity.

     

High prevalence of asthma symptoms in Warao Amerindian children in Venezuela is significantly associated with open-fire cooking: a cross-sectional observational study

Background

The International Study on Asthma and Allergies in Childhood (ISAAC) reported a prevalence of asthma symptoms in 17 centers in nine Latin American countries that was similar to prevalence rates reported in non-tropical countries. It has been proposed that the continuous exposure to infectious diseases in rural populations residing in tropical areas leads to a relatively low prevalence of asthma symptoms. As almost a quarter of Latin American people live in rural tropical areas, the encountered high prevalence of asthma symptoms is remarkable. Wood smoke exposure and environmental tobacco smoke have been identified as possible risk factors for having asthma symptoms.

Methods

We performed a cross-sectional observational study from June 1, 2012 to September 30, 2012 in which we interviewed parents and guardians of Warao Amerindian children from Venezuela. Asthma symptoms were defined according to the ISAAC definition as self-reported wheezing in the last 12 months. The associations between wood smoke exposure and environmental tobacco smoke and the prevalence of asthma symptoms were calculated by means of univariate and multivariable logistic regression analyses.

Results

We included 630 children between two and ten years of age. Asthma symptoms were recorded in 164 of these children (26%). The prevalence of asthma symptoms was associated with the cooking method. Children exposed to the smoke produced by cooking on open wood fires were at higher risk of having asthma symptoms compared to children exposed to cooking with gas (AOR 2.12, 95% CI 1.18 - 3.84). Four percent of the children lived in a household where more than ten cigarettes were smoked per day and they had a higher risk of having asthma symptoms compared to children who were not exposed to cigarette smoke (AOR 2.69, 95% CI 1.11 - 6.48).

Conclusion

Our findings suggest that children living in rural settings in a household where wood is used for cooking or where more than ten cigarettes are smoked daily have a higher risk of having asthma symptoms.     

Risk factors for hospitalization among adults with asthma: the influence of sociodemographic factors and asthma severity

Background

The morbidity and mortality from asthma have markedly increased since the late 1970s. The hospitalization rate, an important marker of asthma severity, remains substantial.

Methods

In adults with health care access, we prospectively studied 242 with asthma, aged 18–50 years, recruited from a random sample of allergy and pulmonary physician practices in Northern California to identify risk factors for subsequent hospitalization.

Results

Thirty-nine subjects (16%) reported hospitalization for asthma during the 18-month follow-up period. On controlling for asthma severity in multiple logistic regression analysis, non-white race (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1–8.8) and lower income (OR, 1.1 per $10,000 decrement; 95% CI, 0.9–1.3) were associated with a higher risk of asthma hospitalization. The severity-of-asthma score (OR, 3.4 per 5 points; 95%, CI 1.7–6.8) and recent asthma hospitalization (OR, 8.3; 95%, CI, 2.1–33.4) were also related to higher risk, after adjusting for demographic characteristics. Reliance on emergency department services for urgent asthma care was also associated with a greater likelihood of hospitalization (OR, 3.2; 95% CI, 1.0–9.8). In multivariate analysis not controlling for asthma severity, low income was even more strongly related to hospitalization (OR, 1.2 per $10,000 decrement; 95% CI, 1.02–1.4).

Conclusion

In adult asthmatics with access to health care, non-white race, low income, and greater asthma severity were associated with a higher risk of hospitalization. Targeted interventions applied to high-risk asthma patients may reduce asthma morbidity and mortality.     

Epidemiology of asthma and associated factors in an urban Pakistani population: adult asthma study-Karachi

Background

This study was conducted in order to determine the prevalence of asthma and associated risk factors in the adult population of Karachi, Pakistan.

Methods

This multi-stage, cross-sectional survey was conducted from May 2014–August 2015; comprising 1629 adults in 75 randomly selected clusters in Karachi, Pakistan. Definitions included: ‘self-reported asthma’, ‘reversibility in FEV₁^’ and ‘respiratory symptoms and reversibility in FEV₁’.

Results

Prevalence of asthma was 1.8% (self-reported) (95% CI: 1.0–2.6), 11.3% (reversibility in FEV₁) (95% CI: 9.4–13.3) and 6.6% (symptoms and reversibility in FEV₁) (95% CI: 5.1–8.1). Asthmatics were more likely to belong to the age group ≥38?years according to ‘reversibility in FEV₁’ and ‘respiratory symptoms and reversibility in FEV₁’ (AOR: 1.9, 95% CI: 1.2–3.3) and (AOR: 2.1, 95% CI: 1.1–4.2), respectively. Asthmatics were more likely to report history of allergies (AOR: 1.9, 95% CI: 1.2–2.9) and (AOR: 2.8, 95% CI: 1.7–4.8); and were exposed to environmental tobacco smoke (AOR: 1.6, 95% CI: 1.1–2.5) and (AOR: 1.9, 95% CI: 1.1–3.3) according to ‘reversibility in FEV₁’ and ‘respiratory symptoms and reversibility in FEV₁’, respectively. Asthmatics were more likely to report pack years of smoking ≥5 (AOR: 2.3, 95% CI: 1.1–4.7) according to ‘respiratory symptoms and reversibility in FEV₁’.

Conclusion

This study reports a high prevalence of asthma among Pakistani adults and calls for developing appropriate public health policies for prevention and control of asthma in the country. Further studies should be conducted to determine the national prevalence as well as follow-up studies to identify preventable causes for adult asthma.

     

Survey on the impact of comorbid allergic rhinitis in patients with asthma

Background

Allergic rhinitis (AR) and asthma are inflammatory conditions of the airways that often occur concomitantly. This global survey was undertaken to understand patient perspectives regarding symptoms, treatments, and the impact on their well-being of comorbid AR and asthma.

Methods

Survey participants were adults with asthma (n = 813) and parents of children with asthma (n = 806) from four countries each in the Asia-Pacific region and Europe. Patients included in the survey also had self-reported, concomitant AR symptoms. Patients and parents were recruited by telephone interview or by direct interview.

Results

Most patients (73%) had pre-existing symptoms of AR when their asthma was first diagnosed. Shortness of breath (21%) was the most troublesome symptom for adults, and wheezing (17%) and coughing (17%) the most troublesome for children. Patients used different medications for treating asthma (most commonly short-acting β-agonists and inhaled corticosteroids) and for treating AR (most commonly oral antihistamines). The concomitant presence of AR and asthma disrupted the ability to get a good night's sleep (79%), to participate in leisure and sports activities (75%), to concentrate at work or school (69% of adults, 73% of children), and to enjoy social activities (57% of adults, 51% of children). Most patients (79%) reported worsening asthma symptoms when AR symptoms flared up. Many (56%) avoided the outdoors during the allergy season because of worsening asthma symptoms. Many (60%) indicated difficulty in effectively treating both conditions, and 72% were concerned about using excessive medication. In general, respondents from the Asia-Pacific region reported more disruption of activities caused by symptoms and more concerns and difficulties with medications than did those from Europe. Differences between the two regions in medication use included more common use of inhaled corticosteroids in Europe and more common use of Chinese herbal remedies in the Asia-Pacific region.

Conclusion

Results of this survey suggest that comorbid asthma and AR substantially impact patient well-being and that the worsening of AR symptoms in patients with asthma can be associated with worsening asthma symptoms. These findings underscore the need for physicians who treat patients with asthma to evaluate treatment options for improving symptoms of both AR and asthma when present concomitantly.

     

Respiratory infections precede adult-onset asthma

Background

Respiratory infections in early life are associated with an increased risk of developing asthma but there is little evidence on the role of infections for onset of asthma in adults. The objective of this study was to assess the relation of the occurrence of respiratory infections in the past 12 months to adult-onset asthma in a population-based incident case-control study of adults 21–63 years of age.

Methods/PrincipalFindings

We recruited all new clinically diagnosed cases of asthma (n = 521) during a 2.5-year study period and randomly selected controls (n = 932) in a geographically defined area in South Finland. Information on respiratory infections was collected by a self-administered questionnaire. The diagnosis of asthma was based on symptoms and reversible airflow obstruction in lung function measurements. The risk of asthma onset was strongly increased in subjects who had experienced in the preceding 12 months lower respiratory tract infections (including acute bronchitis and pneumonia) with an adjusted odds ratio (OR) 7.18 (95% confidence interval [CI] 5.16–9.99), or upper respiratory tract infections (including common cold, sinusitis, tonsillitis, and otitis media) with an adjusted OR 2.26 (95% CI 1.72–2.97). Individuals with personal atopy and/or parental atopy were more susceptible to the effects of respiratory infections on asthma onset than non-atopic persons.

Conclusions/Significance

This study provides new evidence that recently experienced respiratory infections are a strong determinant for adult-onset asthma. Reducing such infections might prevent onset of asthma in adulthood, especially in individuals with atopy or hereditary propensity to it.     

Association between infant feeding patterns and diarrhoeal and respiratory illness: A cohort study in Chittagong, Bangladesh

Background

In developing countries, infectious diseases such as diarrhoea and acute respiratory infections are the main cause of mortality and morbidity in infants aged less than one year. The importance of exclusive breastfeeding in the prevention of infectious diseases during infancy is well known. Although breastfeeding is almost universal in Bangladesh, the rates of exclusive breastfeeding remain low. This cohort study was designed to compare the prevalence of diarrhoea and acute respiratory infection (ARI) in infants according to their breastfeeding status in a prospective cohort of infants from birth to six months of age.

Methods

A total of 351 pregnant women were recruited in the Anowara subdistrict of Chittagong. Breastfeeding practices and the 7-day prevalence of diarrhoea and ARI were recorded at monthly home visits. Prevalences were compared using chi-squared tests and logistic regression.

Results

A total of 272 mother-infant pairs completed the study to six months. Infants who were exclusively breastfed for six months had a significantly lower 7-day prevalence of diarrhoea [AOR for lack of EBF = 2.50 (95%CI 1.10, 5.69), p = 0.03] and a significantly lower 7-day prevalence of ARI [AOR for lack of EBF = 2.31 (95%CI 1.33, 4.00), p < 0.01] than infants who were not exclusively breastfed. However, when the association between patterns of infant feeding (exclusive, predominant and partial breastfeeding) and illness was investigated in more detail, there was no significant difference in the prevalence of diarrhoea between exclusively [6.6% (95% CI 2.8, 10.4)] and predominantly breastfed infants [3.7% (95% CI 0.09, 18.3), (p = 0.56)]. Partially breastfed infants had a higher prevalence of diarrhoea than the others [19.2% (95% CI 10.4, 27.9), (p = 0.01)]. Similarly, although there was a large difference in prevalence in acute respiratory illness between exclusively [54.2% (95%CI 46.6, 61.8)] and predominantly breastfed infants [70.4% (95%CI 53.2, 87.6)] there was no significant difference in the prevalence (p = 0.17).

Conclusion

The findings suggest that exclusive or predominant breastfeeding can reduce rates of morbidity significantly in this region of rural Bangladesh.     

Household environmental tobacco smoke and risks of asthma,wheeze and bronchitic symptoms among children in Taiwan

Background

Although studies show that maternal smoking during pregnancy increases the risks of respiratory outcomes in childhood, evidence concerning the effects of household environmental tobacco smoke (ETS) exposure remains inconsistent.

Methods

We conducted a population-based study comprised of 5,019 seventh and eighth-grade children in 14 Taiwanese communities. Questionnaire responses by parents were used to ascertain children''s exposure and disease status. Logistic regression models were fitted to estimate the effects of ETS exposures on the prevalence of asthma, wheeze, and bronchitic symptoms.

Results

The lifetime prevalence of wheeze was 11.6% and physician-diagnosed asthma was 7.5% in our population. After adjustment for potential confounders, in utero exposure showed the strongest effect on all respiratory outcomes. Current household ETS exposure was significantly associated with increased prevalence of active asthma, ever wheeze, wheeze with nighttime awakening, and bronchitis. Maternal smoking was associated with the increased prevalence of a wide range of wheeze subcategories, serious asthma, and chronic cough, but paternal smoking had no significant effects. Although maternal smoking alone and paternal smoking alone were not independently associated with respiratory outcomes, joint exposure appeared to increase the effects. Furthermore, joint exposure to parental smoking showed a significant effect on early-onset asthma (OR, 2.01; 95% CI, 1.00-4.02), but did not show a significant effect on late-onset asthma (OR, 1.17; 95% CI, 0.36-3.87).

Conclusion

We concluded that prenatal and household ETS exposure had significant adverse effects on respiratory health in Taiwanese children.     

Role of exhaled nitric oxide as a predictor of atopy

Background

The fractional exhaled nitric oxide (FeNO) is a quantitative, noninvasive and safe measure of airways inflammation that may complement the assessment of asthma. Elevations of FeNO have recently been found to correlate with allergic sensitization. Therefore, FeNO may be a useful predictor of atopy in the general population. We sought to determine the diagnostic accuracy of FeNO in predicting atopy in a population-based study.

Methods

We conducted a cross-sectional study in an age- and sex- stratified random sample of 13 to 15 year-olds in two communities in Peru. We asked participants about asthma symptoms, environmental exposures and sociodemographics, and underwent spirometry, assessment of FeNO and an allergy skin test. We used multivariable logistic regression to model the odds of atopy as a function of FeNO, and calculated area-under-the-curves (AUC) to determine the diagnostic accuracy of FeNO as a predictor of atopy.

Results

Of 1441 recruited participants, 1119 (83%) completed all evaluations. Mean FeNO was 17.6 ppb (SD=0.6) in atopics and 11.6 ppb (SD=0.8) in non-atopics (p<0.001). In multivariable analyses, a FeNO>20 ppb was associated with an increase in the odds of atopy in non-asthmatics (OR=5.3, 95% CI 3.3 to 8.5) and asthmatics (OR=16.2, 95% CI 3.4 to 77.5). A FeNO>20 ppb was the best predictor for atopy with an AUC of 68% (95% CI 64% to 69%). Stratified by asthma, the AUC was 65% (95% CI 61% to 69%) in non-asthmatics and 82% (95% CI 71% to 91%) in asthmatics.

Conclusions

FeNO had limited accuracy to identify atopy among the general population; however, it may be a useful indicator of atopic phenotype among asthmatics.     

Risk of valvular heart disease associated with use of fenfluramine

Background

Estimates of excess risk of valvular heart disease among prior users of fenfluramine and dexfenfluramine have varied widely. Two major forms of bias appear to contribute to this variability and also result in a systematic under-estimation of risk. The first, a form of nondifferential misclassification, is the result of including background, prevalent cases among both exposed and unexposed persons in calculations of risk. The second bias results from not considering the relatively short duration of exposure to drugs.

Methods

We examined data from all available echocardiographic studies reporting the prevalence of aortic regurgitation (AR) and mitral regurgitation (MR) among persons exposed to fenfluramine or dexfenfluramine and a suitable control group. We also included one study in which previously existing AR or MR had been excluded. We corrected for background prevalent cases, estimated incidence rates in unexposed persons, and performed a person-years analysis of apparent incidence rates based on exposure time to provide an unbiased estimate of relative risk.

Results

Appearance of new AR was strongly related to duration of exposure (R² = 0.75, p < 0.0001). The summary relative risk for mild or greater AR was 19.6 (95% CI 16.3 – 23.5, p < 0.00001); for moderate or greater MR it was 5.9 (95% CI 4.0 – 8.6, p < 0.00001).

Conclusion

These findings provide strong support for the view that fenfluramine and dexfenfluramine are potent causal factors in the development of both aortic and mitral valvular heart disease.     

Bacterial Exposures and Associations with Atopy and Asthma in Children

Background

The increase in prevalence of asthma and atopic diseases in Western countries has been linked to aspects of microbial exposure patterns of people. It remains unclear which microbial aspects contribute to the protective farm effect.

Objective

The objective of this study was to identify bacterial groups associated with prevalence of asthma and atopy, and to quantify indoor exposure to some of these bacterial groups.

Methods

A DNA fingerprinting technique, denaturing gradient gel electrophoresis (DGGE), was applied to mattress dust samples of farm children and control children in the context of the GABRIEL Advanced study. Associations between signals in DGGE and atopy, asthma and other allergic health outcomes were analyzed. Quantitative DNA based assays (qPCR) for four bacterial groups were applied on the dust samples to seek quantitative confirmation of associations indicated in DNA fingerprinting.

Results

Several statistically significant associations between individual bacterial signals and also bacterial diversity in DGGE and health outcomes in children were observed. The majority of these associations showed inverse relationships with atopy, less so with asthma. Also, in a subsequent confirmation study using a quantitative method (qPCR), higher mattress levels of specifically targeted bacterial groups - Mycobacterium spp., Bifidobacteriaceae spp. and two different clusters of Clostridium spp. - were associated with a lower prevalence of atopy.

Conclusion

DNA fingerprinting proved useful in identifying bacterial signals that were associated with atopy in particular. These findings were quantitatively confirmed for selected bacterial groups with a second method. High correlations between the different bacterial exposures impede a clear attribution of protective effects to one specific bacterial group. More diverse bacterial flora in mattress dust may link to microbial exposure patterns that protect against development of atopic diseases.     

Gastrointestinal Symptoms are Still Prevalent and Negatively Impact Health-Related Quality of Life: A Large Cross-Sectional Population Based Study in The Netherlands

Background

Over the last decades important risk factors for gastrointestinal symptoms have shifted, which may have changed its population prevalence. The aim of this study was to assess the current prevalence of gastrointestinal symptoms, appraise associated factors and assess health-related quality of life in the general population.

Methods

A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Demographic characteristics, gastrointestinal symptoms, health-related quality of life, medication use and co-morbidity were reported. We used multivariable logistic regression analysis to determine factors associated with gastrointestinal symptoms.

Results

A total of 18,317 questionnaires were returned, and 16,758 were eligible for analysis. Prevalence of gastrointestinal symptoms was 26%. Most frequent symptoms were bloating (63%), borborygmi (60%) and flatulence (71%). Female gender (adjusted OR (aOR) 1.59, 95% CI 1.43–1.77), asthma/COPD (aOR 1.47, 95% CI 1.21–1.79), use of paracetamol (aOR 1.33, 95% CI 1.20–1.47), antidepressants (aOR 1.56, 95% CI 1.22–2.00) and acid-suppressive medication were independently associated with presence of gastrointestinal symptoms. Age over 65 years (aOR 0.75, 95% CI 0.65–0.87), and use of statins (aOR 0.75, 95% CI 0.61–0.93) were associated with a lower prevalence of gastrointestinal symptoms. Respondents with gastrointestinal symptoms had a lower mean health-related quality of life of 0.81 (SD = 0.21) compared to 0.92 (SD = 0.14) for persons without gastrointestinal symptoms (P<0.01).

Conclusions

Prevalence of gastrointestinal symptoms in the Dutch community is high and associated with decreased health-related quality of life.     

Advanced age, altered level of consciousness and a new diagnosis of diabetes are independently associated with hypernatreamia in hyperglycaemic crisis

Background

There is limited literature on hypernatreamia in the setting of hyperglycaemic crisis. This is despite the fact that the presence of hypernatreamia may impact on the classification of hyperglycaemic crisis and its management particularly with regards to the nature of fluid therapy. We determined the prevalence of hypernatreamia and its associated factors at presentation for hyperglycaemic crisis.

Methods

This was a retrospective review of data for hyperglycaemic crisis admissions in Nelson Mandela Academic Hospital, Mthatha, South Africa. The prevalence of hypernatreamia (uncorrected Serum Sodium at presentation >145 mmol/L) was determined. Hyperosmolality was defined by calculated effective osmolality >320 mosmols/Kg. Multivariate logistic regression was undertaken using variables that were statistically significant in univariate analysis to ascertain those that were independently associated (Odds Ratio (OR) with 95% Confidence Interval (CI)) with hypernatreamia.

Results

The prevalence of hypernatreamia in our admissions for hyperglycaemic crisis was 11.7% (n = 32/273 including 171 females and 102 males). All admissions with hypernatreamia met the criteria for hyperosmolality. Age ≥ 60 years (OR = 3.9 95% CI 1.3-12.3; P = 0.018), Altered level of consciousness (OR = 8.8 95% CI 2.3-32.8; P < 0.001) and a new diagnosis of diabetes (OR = 3.7 95%CI 1.2-11.5; P = 0.025) were independently associated with hypernatreamia.

Conclusion

The prevalence rate of hypernatreamia in hyperglycaemic admissions was high with all hypernatreamic admissions meeting the criteria for hyperosmolality. Advanced age, altered conscious level and a new diagnosis of diabetes were independently associated with hypernatreamia.     

Drug-Resistant Tuberculosis among HIV-Infected Patients Starting Antiretroviral Therapy in Durban, South Africa

Objective

To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa.

Design

Cross-sectional cohort study.

Methods

Consecutive HIV-infected adults (≥18y/o) initiating HIV care were enrolled from May 2007–May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium). Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed.

Results

1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42–150/µl). 267 subjects (26%) reported a prior history of TB and 210 (20%) were receiving TB treatment at enrollment; 191 (18%) subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0–12.4). Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9–30.5) compared to 5.2% (95% CI 2.1–8.9) among those with no prior TB. 5.1% (95% CI 2.4–9.5) had rifampin or rifampin plus INH resistance.

Conclusions

The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.     

Another explanation for the low allergy rate in the rural Alpine foothills

Background

IL4/IL4RA pathway plays an important role in atopy and asthma. Different polymorphisms in IL4 and IL4RA genes have been described. Particularly, -33C>TIL4 and 576Q>RIL4RA SNPs have been independently associated to atopy and asthma. The purpose of this study was to analyse these polymorphisms in a population of patients with a well-characterized asthma phenotype.

Methods

A total of 212 unrelated Caucasian individuals, 133 patients with asthma and 79 healthy subjects without symptoms or history of asthma or atopy and with negative skin prick tests were recruited. Lung function was measured by spirometry and asthma was specialist physician-diagnosed according to the ATS (American Thoracic Society) criteria and classified following the GINA (Global Initiative for Asthma) guidelines. Skin prick tests were performed according to EAACI recommendations. -33C>TIL4 was studied with TaqMan assay and 576Q>RIL4RA by PCR-RFLP technique. Hardy-Weinberg equilibrium was analysed in all groups. Dichotomous variables were analysed using χ², Fisher exact test, Monte Carlo simulation test and odds ratio test. To model the effects of multiple covariates logistic regression was used.

Results

No statistically significant differences between the group of patients with asthma and the controls were found when the allele and genotype distribution of -33C>TIL4 and 576Q>RIL4RA polymorphisms were compared. However, the T allele of the -33C>TIL4 SNP was more frequent in patients with persistent asthma. Multivariate analysis adjusted for age and sex confirmed that carriers of allele T had an increased risk of persistent asthma (OR:2.77, 95%CI:1.18–6.49; p = 0.019). Analysis of combination of polymorphisms showed that patients carrying both the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA had an increased risk of asthma. This association was particularly observed in persistent asthma [Fisher's p value = 0.0021, Monte Carlo p value (after 10⁴ simulations) = 0.0016, OR:3.39; 95% CI:1.50–7.66].

Conclusion

Our results show a trend of association between the genetic combination of the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA with asthma. This genetic variant was more frequently observed in patients with persistent asthma. As long as this study was performed in a small population, further studies in other populations are needed to confirm these results.     

Prevalence of inherited ichthyosis in France: a study using capture-recapture method

Background

Inherited ichthyoses represent a group of rare skin disorders characterized by scaling, hyperkeratosis and inconstant erythema, involving most of the tegument. Epidemiology remains poorly described. This study aims to evaluate the prevalence of inherited ichthyosis (excluding very mild forms) and its different clinical forms in France.

Methods

Capture – recapture method was used for this study. According to statistical requirements, 3 different lists (reference/competence centres, French association of patients with ichthyosis and internet network) were used to record such patients. The study was conducted in 5 areas during a closed period.

Results

The prevalence was estimated at 13.3 per million people (/M) (CI95%, [10.9 – 17.6]). With regard to autosomal recessive congenital ichthyosis, the prevalence was estimated at 7/M (CI 95% [5.7 – 9.2]), with a prevalence of lamellar ichthyosis and congenital ichthyosiform erythroderma of 4.5/M (CI 95% [3.7 – 5.9]) and 1.9/M (CI 95% [1.6 – 2.6]), respectively. Prevalence of keratinopathic forms was estimated at 1.1/M (CI 95% [0.9 – 1.5]). Prevalence of syndromic forms (all clinical forms together) was estimated at 1.9/M (CI 95% [1.6 – 2.6]).

Conclusions

Our results constitute a crucial basis to properly size the necessary health measures that are required to improve patient care and design further clinical studies.     

Early gene expression changes with rush immunotherapy

Background

Allergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied.

Objective

To test for associations between variants in TSLP, TSLP -related genes, and AR in children with asthma.

Methods

We genotyped 15 single nucleotide polymorphisms (SNPs) in TSLP, OX40L, IL7R, and RXRα in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for TSLP, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.

Results

Across the three cohorts, the T allele of TSLP SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fisher's combined P value of 1.2 × 10^-4). Our findings were significant after accounting for multiple comparisons. SNPs in OX40L, IL7R, and RXRα were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.

Conclusions

TSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for TSLP in the pathogenesis of AR in children with asthma.