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THE IRISH ISAAC STORY

The Irish ISAAC team consisted of Prof Luke Clancy as Principal Investigator and the national coordinator Dr Pat Manning, with technical inputs from Prof Patrick Goodman and Dr Zubair Kabir and Sheila Keogan (all based in Dublin). Ireland participated in two phases of the ISAAC study- Phase 1 in 1995 and Phase 3 in 2002/2003. ‘Wave 2’ was a follow-up on Phase 1 in 1998 and ‘Wave 4’ was follow-up on Phase 3 in 2007 and was done in collaboration with the Asthma Society of Ireland headed-up by Dr Jean Holohan. Ireland had only one centre, St. James’s Hospital based in Dublin. A target of ~3000 respondents was aimed for in the probability multi-stage sampling of post-primary schools all across Ireland in all 4 surveys. Participation rates were high (>80%) and the response rates were also high (>90%) in both the Phases. A few schools did not participate and a few were closed in Phase 3 and therefore so some new schools were included in Phase 3 compared to Phase 1. Only one age group of school children between 13 and 14 years were recruited for both the Phases. The study findings were disseminated through various platforms- presentations in annual scientific meetings (both national and internationally- such as the Irish Thoracic Society Meetings and the European Respiratory Society Meetings). A few high quality publications were also published in international medical journals. Following is the list of publications from each Phase of the ISAAC study in Ireland, including key messages of each individual publication.

Following publications arose from Phase I study

1. Asthma, hay fever and eczema in Irish teenagers (ISAAC protocol).
   Manning PJ, Curran K, Kirby B, Taylor MR, Clancy L.
   Ir Med J. 1997 Apr-May; 90(3):110-2.

The prevalence values for asthma, hay fever and eczema were 15.2%, 24.8% and 9.4% respectively. Although 5.4% reported having asthma and hay fever, combinations of the other allergic conditions were less than 2%. Sex difference in prevalence rates for the various conditions occurred with asthma prevalence being higher for males, eczema in females, but hay fever was almost equally reported between males and females.

2. Smoking, atopy and certain furry pets are major determinants of respiratory symptoms in children: the International Study of Asthma and Allergies in Childhood Study (Ireland).
   Yarnell JW, Stevenson MR, MacMahon J, Shields M, McCrum EE, Patterson CC, Evans AE, Manning PJ, Clancy L.
   Clin Exp Allergy. 2003 Jan; 33(1):96-100.

Questionnaires were completed by 2,364 children from Northern Ireland and 2,671 from the Republic- about 90% of those eligible to participate. The prevalences of wheeze at various levels of severity, of diagnosed asthma and of treated wheeze were very similar in Northern Ireland and the Republic of Ireland. A significant proportion of those reporting more severe symptomatology (four or more attacks of wheeze in the past 12 months and/or one or more nights disturbed and/or moderate or greater disruption of daily activities and/or speech restriction due to wheeze) had been neither diagnosed nor treated for asthma (20-37%). To investigate the determinants of the more severe symptomatology of asthma or treated wheeze a series of stepwise multiple regression analyses was performed. A history of atopy, cigarette smoking, and possession of a furry pet other than a dog or cat and age were each independently associated with severe wheeze, whilst atopy, a furry pet (as above) and gender were each independently associated with asthma or treated wheeze. Cigarette smoking is closely associated with the reporting of significant respiratory symptoms together with atopy and exposure to furry pets. Some 20-37% of severe symptoms were neither diagnosed nor treated as asthma.

The following publication arose from Phase 1 and Wave 2

1. Bronchitis symptoms in young teenagers who actively or passively smoke cigarettes.
   Manning P, Goodman P, Kinsella T, Lawlor M, Kirby B, Clancy L
   Ir Med J. 2002 Jul-Aug; 95(7):202-4.

This study was undertaken to examine the prevalence of bronchitis (cough with phlegm) symptoms in teenagers who either smoked cigarettes on a regular basis (active smokers) or were non-smokers but who are exposed to passive smoking (passive smokers) in the home. The study was undertaken in 1995 and repeated in 1998. The 1995 study was a cross sectional questionnaire survey of smoking habits in secondary school children aged 13-14 years and was undertaken as part of the ISAAC questionnaire survey. Thirty representative and randomly selected schools from throughout the Republic of Ireland took part in the study. In the 1995 study, 3066 students completed a questionnaire on their current smoking habits and symptoms of cough and phlegm. We found that 634 (20.7%) of these young teenagers actively smoked cigarettes with significantly more females smoking than males with 23.3% of girls compared to 17.6% boys (p = 0.0001). We found that 46.3% of non-smoking children were exposed to smoking in the home (passive smokers) with parental smoking accounting for most of the passive smoking. Bronchitis symptoms were more commonly reported in active smokers compared to non-smokers with an odds ratio of 3.02 (95% CI 2.34-3.88) (p < 0.0001) or in passive smokers compared to those not exposed to smoking with odds ratio of 1.82 (95% CI 1.32-2.52) (p < 0.0001). The 1998 study showed similar results for smoking habits, passive smoking and prevalence of bronchitis symptoms as with the 1995 study. These results document that increased bronchitis symptoms occur in teenagers exposed to active or passive smoking.

The following publication arose from Phase 1 and Phase 3:

1. Rising prevalence of asthma but declining wheeze in teenagers (1995-2003): ISAAC protocol.
   Manning PJ, Goodman P, O'Sullivan A, Clancy L.
   Ir Med J. 2007 Nov-Dec; 100(10):614-5.

The results of the initial International Study of Asthma and Allergies in Childhood (ISAAC) undertaken in the mid 1990s demonstrated a substantial increase in asthma and wheeze symptoms prevalence in Irish teenagers aged 13-14 years from the 1980s. International research suggests that asthma has increased further in some countries and this study was undertaken to determine whether an upward trend in childhood asthma prevalence had continued in the Republic of Ireland in recent years. We therefore conducted two further national cross sectional studies in the same previously surveyed childhood population throughout the Republic of Ireland, one in 1998 (n=2580) and the other in 2002-3 (n=3089). We reported here on rising prevalence trends of asthma (42.1% relative increase) but falling wheeze (10.4% relative reduction) prevalence in these teenage children in 2002-3.

Wave 4 was the final study and was conducted in 2007 as a follow-up on Phase 3. Some interesting question, for example, the inclusion of questions related to smoking in cars was found useful and was unique.

The following publications arose from Wave 4, including analyses from previous Phases:

1. Second hand smoke exposure - in cars and respiratory health effects in children.
   Kabir Z, Manning PJ, Holohan J, Keogan S, Goodman PG, Clancy L.
   Eur Respir J. 2009 Sep; 34(3):629-33.

Overall, 14.8% (13.9% in young males, 15.4% in young females) of Irish children aged 13-14 yrs old were exposed to SHS in cars. Although there was a tendency towards increased likelihood of both respiratory and allergic symptoms with SHS exposure in cars, wheeze and hay fever symptoms were significantly higher (adjusted OR 1.35 (95% CI 1.08-1.70) and 1.30 (1.01-1.67), respectively), while bronchitis symptoms and asthma were not significant (1.33 (0.92-1.95) and 1.07 (0.81-1.42), respectively). Approximately one in seven Irish schoolchildren is exposed to SHS in cars and could have adverse respiratory health effects. Further studies are imperative to explore such associations across different population settings.

2. Active smoking and second-hand-smoke exposure at home among Irish children, 1995-2007.
   Kabir Z, Manning PJ, Holohan J, Goodman PG, Clancy L.
   Arch Dis Child. 2010 Jan; 95(1):42-5

There were significant reductions in active smoking rates between 1995 and 2007 (from 19.9% to 10.6%, respectively) resulting in 3.3% survey-to-survey reductions, with a significantly greater survey-to-survey decline among girls compared to boys (3.8% vs 2.7%, respectively). 45% of children were exposed to SHS at home in 2007. There was a statistically non-significant 2% overall decline in SHS exposure levels at home in 2007 relative to 2002/03, which was more pronounced in girls. The continual reduction in active smoking prevalence in children is welcome. That there was no significant increase in SHS exposure at home after the nationwide workplace smoking ban suggesting that the ban did not increase smoking inside homes as had been feared.

3. Prevalence of Symptoms of Severe Asthma and Allergies in Irish School Children: An ISAAC Protocol Study, 1995-2007.
   Kabir Z, Manning PJ, Holohan J, Goodman PG, Clancy L.
   Int J Environ Res Public Health. 2011 Aug; 8(8):3192-201.

Childhood asthma is a recurring health burden and symptoms of severe asthma in children are also emerging as a health and economic issue. This study examined changing patterns in symptoms of severe asthma and allergies (ever eczema and hay fever). Children aged 13-14 years were studied: 2,670 (in 1995), 2,273 (in 1998), 2,892 (in 2002-2003), and 2,805 (in 2007). Generalized linear modelling using Poisson distribution was employed to compute adjusted prevalence ratios (PR). A 39% significant increase in symptoms of severe asthma was estimated in 2007 relative to the baseline year 1995 (adjusted PR: 1.39 [95% CI: 1.14-1.69]) increasing from 12% in 1995 to 15.3% in 2007. Opposite trends were observed for allergies, showing a decline in 2007, with an initial rise. The potential explanations for such a complex disease pattern whose aetiological hypothesis is still evolving are speculative. Changing environmental factors may be a factor, for instance, an improvement in both outdoor and indoor air quality further reinforcing the hygiene hypothesis but obesity as a disease modifier must also be considered.

Funding: Royal City of Dublin Hospital Trust; Health Research Board of Ireland