Medical Journal Review
Posted: July 2010
Reviewed by Juan Carlos Ivancevich, MD, in collaboration with Phil Lieberman, MD.
1. A new score constructed to predict asthma exacerbations in children.
The authors aimed to construct a clinical score to help providers with identifying asthmatic children at risk for exacerbations. The main outcome was severe asthma exacerbations, defined as: any hospitalization, urgent visit, or systemic steroid course for asthma in the previous year. The researchers built and validated a clinical score (including asthma symptoms, use of medications and healthcare, and past history) in a cross-sectional study of asthmatic children in Costa Rica. It was then evaluated using data from the Childhood Asthma Management Program (CAMP), a longitudinal cohort of North American children. The clinical score is a checklist-type questionnaire with 17 yes or no questions. Compared to children at average risk in the Costa Rican validation set, the odds of an exacerbation among children in the low- (OR=0.2, 95% CI =0.1-0.4) and high-risk (OR=5.4, 95% CI=1.5-19.2) score categories were significantly reduced and increased, respectively. In CAMP, the hazard ratios for an exacerbation after 1 year of follow-up in the low- and high-risk groups were 0.6 (95% CI=0.5-0.7) and 1.9 (95% CI=1.4-2.4), respectively, with similar results at 2 years. The authors concluded that the proposed Asthma Exacerbation Clinical Score is simple to use and effective at identifying children at high- and low-risk for asthma exacerbations, and can easily be used in primary care settings.
Editor's comment: Primary care providers now have efficient tools to identify asthmatic children at high risk for exacerbations.
Forno E, Fuhlbrigge A, Soto-Quirós ME et al, Risk factors and predictive clinical score for asthma exacerbations in childhood. Chest 2010; published online before print May 14 (chest.09-2426)
2. Maternal repletion with vitamin A (VA) at recommended dietary levels before, during, and after pregnancy improved lung function in offspring.
The authors tested the hypothesis that maternal vitamin A (VA) status may be an important determinant of embryonic alveolar formation, and that VA deficiency in a mother during pregnancy could have lasting adverse effects on the lung health of her offspring. To do so they examined the long-term effects of supplementation with VA or beta carotene (bc) in women before, during, and after pregnancy on the lung function of their offspring, in a population with chronic VA deficiency. They examined a cohort of rural Nepali children 9 to 13 years of age whose mothers had participated in a Double-Blind Placebo-Controlled (DBPC) cluster-randomized trial of VA or bc supplementation between 1994 and 1997. Of 1,894 children who were alive at the end of the original trial, 1,658 (88%) were eligible to participate in the follow-up trial. The authors performed spirometry in 1,371 of the children (83% of those eligible) between October 2006 and March 2008. Children whose mothers had received VA had a FEV1 and FVC significantly higher than those of children whose mothers had received placebo. Children whose mothers had received bc had adjusted FEV1 and FVC values that were similar to those of children whose mothers had received placebo.
Editor's comment: Vitamin A is important in regulating early lung development and alveolar formation.
Checkley W, West KP Jr, Wise RA et al, Maternal Vitamin A Supplementation and Lung Function in Offspring. New England Journal of Medicine 2010; 362(19): 1784-1794.
3. Guidelines for asthma controller therapy in children in the United Kingdom (UK) 'not always followed.
The authors used the "UK General Practice Research Database" to study 10,004 children (59.4% boys), aged 8 years on average, who were treated for asthma or recurrent wheezing between 2006 and 2007. Physicians who treated 635 randomly selected patients from the cohort were asked to complete a questionnaire retrospectively classifying asthma severity at the time of the prescription date and for the 6-month period prior to the index date using the patients' records. The researchers found that 9,059 (90.6%) children were prescribed inhaled corticosteroids (ICS) as monotherapy, 698 (7.0%) were prescribed ICSs plus a long-acting beta agonist (LABA), 91 (0.9%) were prescribed leukotrine receptor antagonists (LTRA) monotherapy, and 55 (0.6%) were prescribed ICSs plus an LTRA. A further 101 (1.0%) children were prescribed other types of therapy, including LABA monotherapy (n=45; 0.45%). Forty-four (2.1%) of 2,140 children aged less than 5 years were prescribed high-dose ICSs (>400 µg), compared with 420 (5.6%) of 7,452 children aged 5 years or older. The authors conclude that physician classifications of asthma severity did not always correspond to guideline recommendations for prescribing controller therapy. In UK primary care, despite endorsement in local guidelines, children with asthma are seldom treated with an LTRA, and monotherapy with ICSs is the most common controller therapy at all levels of severity.
Editor's comment: Monotherapy with ICSs is the most common controller therapy at all levels of asthma severity in UK children, and LTRAs are rarely prescribed.
Thomas M, Murray-Thomas T, Fan T et al, Prescribing patterns of asthma controller therapy for children in UK primary care: A cross-sectional observational study. BMC Pulmonary Medicine 2010 May 14; 10:29.
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4. Effective, non-indoor polluting heating reduces school absence for asthmatic children.
The aim of this study was to determine whether more effective home heating affects school absence for children with asthma. New Zealand homes are under heated by international standards, with average indoor temperatures below the World Health Organization (WHO) recommended minimum of 18°C. Both health effects and social effects can impact on school absentee rates. A single-blinded, randomized controlled trial of heating intervention in 409 households containing an asthmatic child aged 6-12 years, where the previous heating was an open fire, plug-in electric heater or unflued gas heater. The intervention was the installation of a more effective heater of at least 6 kilowatts (kW) before the winter of 2006 in half the houses. Demographic and health information was collected both before and after the intervention. Each child's school was contacted directly and term-by-term absenteism information for that child was obtained for 2006 and previous years where available. Complete absentee data were obtained for 269 out of 409 children. Compared with the control group, children in households receiving the intervention experienced on average 21% (p=0.02) fewer days of absence after allowing for the effects of other factors. More effective, non-indoor polluting heating reduces school absence for asthmatic children.
Editor's comment: There is a connection between low indoor temperatures and adverse health outcomes.
Free S, Howden-Chapman P, Pierse N et al, More effective home heating reduces school absences for children with asthma. Journal of Epidemiology and Community Health 2010; 64(5):379-386.
5. Half of patients with occupational asthma (OA) caused by exposure to ammonium persulphate (AP) also have occupational rhinitis (OR).
To compare the clinical and inflammatory features of occupational asthma (OA) -only and OA associated to occupational rhinitis (OAR) the authors reviewed the clinical charts of patients diagnosed with respiratory allergy caused by ammonium persulfate (AP), confirmed by specific inhalation challenge (SIC). Of 26 patients, 12 were diagnosed as OA-only and 14 with OAR. There were no significant differences between groups in personal and occupational risk factors, duration of exposure before diagnosis, latency period between the beginning of exposure and asthma symptom onset, basal FEV1, airway reactivity to methacholine, or asthma severity. Both groups had eosinophilic inflammation of upper and lower airways. In 22 patients who underwent a pre-SIC-induced sputum challenge test, eosinophil percentage tended to be higher with OAR (11.9%) than with OA-only (2.95%), but was not statistically so. Eosinophilia in nasal secretions was present in 55% of OAR patients and 38% of OA-only patients, again representing a nonsignificant between-group difference. The presence of rhinitis did not seem to have any impact on the natural history of asthma. Irrespective of the presence of rhinitis, eosinophilic nasal inflammation was detectable in all subjects and may be considered as the expression of the united airways disease (UAD) concept in persulfate occupational allergy.
Editor's comment: The high frequency of association between OA and OR supports the UAD concept in occupational respiratory allergy.
Moscato G, Pala G, Perfetti L et al, Clinical and inflammatory features of occupational asthma caused by persulphate salts in comparison with asthma associated with occupational rhinitis. Allergy 2010; 65(6): 784-790.
6. Recent advances noted in the understanding of the laryngeal effects of allergies with particular attention to the impact on vocal production.
A growing body of literature suggests an association between allergies and dysphonia evidenced by the increased likelihood of singers with vocal complaints to self-identify allergic rhinitis by standardized questionnaire compared with singers without vocal complaints, the severity of vocal symptoms of allergic patients in relationship to nonallergic controls, and the increased vocal complaints of allergic individuals from the nonallergy to allergy seasons. Arguments have also been made for the misdiagnosis of allergic dysphonia as laryngopharyngeal reflux disease. A recent study has demonstrated the first evidence of a causal relationship between allergen exposure and voice changes in the absence of a sinus or lower airway allergic response. The existence of a direct allergic response in the larynx has meaningful implications for the diagnosis and treatment of dysphonia. Further research is needed to identify the underlying pathways mediating the laryngeal response to allergy so that improved diagnostic and therapeutic techniques can be developed.
Editor's comment: New evidence has highlighted the likelihood that allergies are indeed associated with dysphonia.
Roth D and Ferguson BJ, Vocal allergy: recent advances in understanding the role of allergy in dysphonia. Current Opinion in Otolaryngology & Head and Neck Surgery 2010; 18(3): 176-181.
7. Inhaled corticosteroids studied as anti-inflammatory drugs preventing atherosclerosis.
Carotid atherosclerosis (CA) was evaluated by ultrasonography in 150 asthmatic patients who had been regularly treated with inhaled corticosteroids and in 150 matched controls, with an assessment of atherosclerotic risk factors. Carotid intima-media thickness was significantly lower in the asthmatic patients than in the controls. The prevalence of carotid plaque tended to be lower in the asthmatic patients than that in the controls. Defined CA was diagnosed in 51 of the asthmatic patients who were older, more in males, and had higher prevalence of dyslipidemia and a lower mean daily dose of inhaled corticosteroids than the other 99 patients without CA. Stepwise multiple logistic regression analysis demonstrated that age, male sex, and dyslipidemia were identified as positive risk factors for CA, whereas the mean daily dose of inhaled corticosteroids proved to be a negative risk factor. CA was reduced in asthmatic patients treated with inhaled corticosteroids, compared with matched controls. The present study suggests that inhaled corticosteroids may have protective effects against atherosclerosis.
Editor's comment: Inhaled corticosteroids appear to lower the risk of carotid atherosclerosis in asthmatics, presumably via their anti-inflammatory effect.
Otsuki M, Miyatake A, Fujita K et al. Reduced carotid atherosclerosis in asthmatic patients treated with inhaled corticosteroids. European Respiratory Journal, 2010 April 22 [Epub ahead of print].
8. Relationship examined between obstructive sleep apnea (OSA) risk and asthma control in adults.
To assess this relationship, asthma patients at routine tertiary care clinic visits completed the validated Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ) and Asthma Control Questionnaire (ACQ). ACQ ?1.5 defined not well controlled asthma, and SA-SDQ ?36 for men and ?32 for women defined high risk of obstructive sleep apnea (OSA). Logistic regression was used to model associations of high OSA risk with not well controlled asthma (ACQ full and short versions). Among 472 subjects with asthma, the mean ACQ (full version) score was 0.87±0.90 and 80 subjects (17%) were not well controlled. Mean SA-SDQ score was 27±7, and 109 subjects (23%) met the definition of high OSA risk. High OSA risk was associated on average with 2.87 times higher odds for not well controlled asthma (ACQ full version) (95% confidence interval [1.54-5.32], p=0.0009), after adjusting for obesity and other factors known to worsen asthma control. Similar independent associations were seen when using the short ACQ versions. The authors concluded that high OSA risk is significantly associated with not well controlled asthma, independent of known asthma aggravators and regardless of the ACQ version used. Patients who have difficulty achieving adequate asthma control should be screened for OSA.
Editor's comment: Unrecognized obstructive sleep apnea may lead to poor asthma control despite optimal therapy.
Teodorescu M, Polomis DA, Hall SV et al, Association of Obstructive Sleep Apnea Risk with Asthma Control in Adults. Chest 2010; published online before print May 21 (chest.09-3066)
9. Nasal eosinophilia: an indicator of eosinophilic inflammation in asthma.
The aim of this study was to compare the eosinophil counts in induced sputum and nasal lavage fluids in asthma, checking their association and the accuracy of nasal eosinophilia (ne) as a predictor of sputum eosinophilia (se) by a cross-sectional study. The clinical evaluation, asthma control questionnaire (ACQ), pre- and post-bronchodilator spirometry, nasal and sputum sample was performed. The ne was analyzed by a receiver operating curve and logistic regression model. In 140 adults, the post-bronchodilator FEV1 did not differ between patients with or without se (0.18). After adjusted for upper airway symptoms, age, ACQ score and post-bronchodilator FEV1, se was associated with a 52 times increase in odds of ne, whereas each 1% increase in bronchodilator response was associated with 7% increase in odds of ne. The authors concluded that this study brings further evidence that upper airway inflammation is an important component of the asthma syndrome. Furthermore, monitoring of ne by quantitative cytology may be useful as a surrogate for sputum cytology, and as a component of a composite measurement for determining airway inflammation.
Editor's comment: There is a clear clinical, epidemiological and pathophysiological association between upper and lower airway inflammation in rhinitis and asthma.
Amorim MM, Araruna A, Caetano LB et al, Nasal eosinophilia: an indicator of eosinophilic inflammation in asthma. Clinical & Experimental Allergy 2010; 40(6): 867-874.
10. Effects of prenatal environmental exposures on adult offspring in mouse studies.
The effects of prenatal environmental exposures on adult offspring have not been well-studied. The authors hypothesized that combined prenatal exposure to Aspergillus fumigatus (A. fumigatus) allergen and diesel exhaust particles will be associated with altered IgE production, airway inflammation, airway hyperreactivity (AHR), and airway remodeling of adult offspring. Following sensitization via airway route to A. fumigatus and mating, pregnant BALB/c mice were exposed to additional A. fumigatus and/or diesel exhaust particles. At age 9-10 weeks, their offspring were sensitized and challenged with A. fumigatus. They found that adult offspring from mice that were exposed to A. fumigatus or diesel exhaust particles during pregnancy experienced decreases in IgE production. Adult offspring of mice that were exposed to both A. fumigatus and diesel exhaust particles during pregnancy experienced decreases in airway eosinophilia. These results suggest that, in this model, allergen and/or diesel administration during pregnancy may be associated with protection from developing systemic and airway allergic immune responses in the adult offspring.
Editor's comment: Although studies have suggested that prenatal exposure to allergens or air pollution may increase the risk for the development of allergic immune responses in young offspring, this study concludes otherwise.
Lin L, Zhu H, Quan C et al, Prenatal allergen and diesel exhaust exposure and their effects on allergy in adult offspring mice. Allergy, Asthma & Clinical Immunology 2010; 6:7.
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11. Clinical utility of molecular testing for primary immune deficiency disorders (PIDs).
PIDs are a group of diseases associated with a genetic predisposition to recurrent infections, malignancy, autoimmunity and allergy. The molecular basis of many of these disorders has been identified in the last two decades. Most are inherited as single gene defects. Identifying the underlying genetic defect plays a critical role in patient management including diagnosis, family studies, prognostic information, and prenatal diagnosis and is useful in defining new diseases. In this review the authors outline the clinical utility of molecular testing for these disorders using clinical cases referred to Auckland Hospital. The article is written from the perspective of a laboratory offering a wide range of tests for a small developed country.
Editor's comment: Excellent case based review about the clinical utility of molecular testing for PIDs.
Ameratunga R, Woon ST, Neas K et al, The clinical utility of molecular diagnostic testing for primary immune deficiency disorders: a case based review. Allergy, Asthma & Clinical Immunology 2010; 6:12.
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12. Overall efficacy of adeno-tonsillectomy (AT) in treatment of obstructive sleep apnea syndrome (OSAS) in children.
To quantify the effect of demographic and clinical confounders known to impact the success of adeno-tonsillectomy (AT) in treating obstructive sleep apnea syndrome (OSAS), the researchers performed a multicenter, collaborative, retrospective review of all nocturnal-polysomnograms performed both pre- and post-operatively on otherwise healthy children undergoing AT for treating OSAS. The study was performed at 6 pediatric sleep centers in the USA and 2 in Europe. They used multivariate generalized linear modeling to assess contributions of specific demographic factors on the post-AT obstructive apnea hypopnea index (AHI). The authors analyzed data from 578 children (mean age: 6.9±3.8 years), of which approximately 50% were obese. AT resulted in a significant AHI reduction from18.2±21.4 to 4.1±6.4/hrTST (p<0.001). Of the 578 children, only 157 (27.2%) had complete resolution of OSAS (i.e.,post-AT AHI<1/hrTST). Age and BMI z-score emerged as the 2 principal factors contributing to post-AT AHI (p<0.001), with modest contributions due to the presence of asthma and the magnitude of pre-AT AHI (p<0.05) among non-obese children. AT leads to significant improvements in indices of sleep disordered breathing in children. However, residual disease is present in a large proportion of children after AT, particularly among older (>7 years) or obese children.
Editor's comment: Interesting study about factors that promote incomplete resolution of OSAS after AT.
Bhattacharjee R, Kheirandish-Gozal L, Spruyt K et al, Adenotonsillectomy Outcomes in Treatment of OSA in Children: A Multicenter Retrospective Study, American Journal of Respiratory and Critical Care Medicine published ahead of print on May 6, 2010.