This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.

Cord-blood levels of 25(OH)D had inverse associations with risk of respiratory infection and childhood wheezing but no association with incident asthma.

The epidemiological studies cited have indicated that viruses are commonly associated with wheezing illnesses in populations, in individuals, and in time, but, unlike bacteria, are rarely found during asymptomatic periods. Viruses have been identified in up to 50% of wheezing illnesses and asthma exacerbations occurring in childhood, and in up to 20% of those in adults. In childhood the predominant organisms identified have been rhinoviruses. RSV and parainfluenza viruses, but coronaviruses have not been studied adequately. Wheezing appears to be more common during rhinovirus and RSV than other virus infections in children spontaneously presenting with respiratory infections to medical care, but all virus groups have been incriminated, and in general, wheezing occurs in upwards of 50% of viral infections in asthmatics followed prospectively. The few adult studies available show little difference between viruses in identification rates during wheezing, or propensity to result in wheezing. The predominant viruses change with age, and children with asthma seem to be more prone to symptomatic virus infections than other children, although the presence of atopy alone does not appear to be important. There are important gaps in our knowledge of the epidemiology of virus-associated wheezing attacks, and further prospective studies are required, using early investigation and sensitive methods for identifying rhinoviruses and coronaviruses, to study severe asthma in children and adults. It is hoped that the use of nucleic acid hybridization and newer antigen-detection techniques will improve the ability to identify difficult viruses such as coronaviruses and rhinoviruses in the future. The ability to identify subclinical infections and compare the ratio of subclinical to clinical infections in normal and asthmatic children would be useful but would require intense monitoring of both groups for an extended period (minimum 12 months to cover seasonal variation) with full virological studies every 2-4 weeks-a difficult and expensive task. Another important line of study would be to prospectively document indoor aeroallergen exposure and virus infections in the same individuals, and compare their importance as precipitants of acute severe asthma attacks. With a clearer understanding of the groups at risk for asthma attacks, and the factors which put them at risk and precipitate their attacks, effective preventive strategies will become more feasible.

Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community.

BackgroundPseudomonas aeruginosa infections are associated with progressive life threatening decline of lung function in cystic fibrosis sufferers. Growth of Ps. aeruginosa releases a "grape-like" odour that has been identified as the microbial volatile organic compound 2-aminoacetophenone (2-AA).MethodsWe investigated 2-AA for its specificity to Ps. aeruginosa and its suitability as a potential breath biomarker of colonisation or infection by Solid Phase Micro Extraction and Gas Chromatography-Mass Spectrometry (GC/MS).ResultsCultures of 20 clinical strains of Ps. aeruginosa but not other respiratory pathogens had high concentrations of 2-AA in the head space of in vitro cultures when analysed by GC/MS. 2-AA was stable for 6 hours in deactivated glass sampling bulbs but was not stable in Tedlar® bags. Optimisation of GC/MS allowed detection levels of 2-AA to low pico mol/mol range in breath. The 2-AA was detected in a significantly higher proportion of subjects colonised with Ps. aeruginosa 15/16 (93.7%) than both the healthy controls 5/17 (29%) (p < 0.0002) and CF patients not colonised with Ps. aeruginosa 4/13(30.7%) (p < 0.001). The sensitivity and specificity of the 2-AA breath test compared to isolation of Ps. aeruginosa in sputum and/or BALF was 93.8% (95% CI, 67-99) and 69.2% (95% CI, 38-89) respectively. The peak integration values for 2-AA analysis in the breath samples were significantly higher in Ps. aeruginosa colonised subjects (median 242, range 0-1243) than the healthy controls (median 0, range 0-161; p < 0.001) and CF subjects not colonised with Ps. aeruginosa (median 0, range 0-287; p < 0.003)ConclusionsOur results report 2-AA as a promising breath biomarker for the detection of Ps. aeruginosa infections in the cystic fibrosis lung.