Risk factors for asthma at 3.5 and 7 years of age

Mitchell, Edwin A.; Robinson, Elizabeth; Black, Peter; Becroft, D. M. O.; Clark, P.; Pryor, Jan; Thompson, John M. D.; Waldie, Karen E.; Wild, C. J.

doi:10.1111/j.1365-2222.2007.02847.x

Cited by 17 publications

(14 citation statements)

References 52 publications

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“…There were six dissenting studies [41–45], and with respect to one of these, the authors reached the opposite conclusion on a later occasion [46]. Moreover, Mitchell et al [47], while seeing the case for an antibiotic causation strengthened, acknowledged the possibility of confounding by indication. The authors of the remaining study [48] considered both bias and true causation possible, but suggested confounding by indication in a later overview [66].…”

Section: Discussionmentioning

confidence: 99%

“…2) Causal association concluded Prospective Birth Cohort Studies (Cases of interest identified after recruitment)Alm et al [41] (studied age group (until 12 months) does not allow firm conclusions on asthma; no adjustment for respiratory infections, confounding by indication still possible); Risnes et al [42] (interview 6 years after birth, recall bias possible); Goksör et al [43] (broad spectrum antibiotics were considered causative, no details; confounding by indication possible due to lack of information on infectious diagnosis); Jedrychowski et al [44] (when adjusted for respiratory infections, the Odds ratio lost statistical significance; macrolide and cephalosporin associations lost strength, but retained significance; considered that immuno-modulation might underlie asthma promotion by (certain) antibiotics); Marra et al [45] (after excluding children with upper or lower respiratory infection the hazard ratio still showed a small association between antibiotics and asthma (but cf. Marra et al [46], below)); Causal association as well as confounding by indication considered Mitchell et al [47] (no adjustment for airway infections; concluded that antibiotics are a risk factor but considered confounding by respiratory infections); Kummeling et al [48] (no adjustment for airway infections; in a later overview, the same authors suggested confounding by indication (Kummeling and Thijs [66])) Association explained by confounding factors or no associations found Marra et al [46] (considered that antibiotics were used for asthmatic wheeze (reverse causation)); Kusel et al [49] (concluded that the data did not indicate that using antibiotics early in life led to asthma at 5 years; cf. Fig.…”

Section: Factors That Might Set the Stage For Asthma Developmentmentioning

confidence: 99%

“…Mitchell et al [47] felt that their data strengthened the hypothesis of a causal relationship, but acknowledged the possibility of confounding by indication. In the second further study, the possibilities of causation and of confounding by indication were given similar weights [48].…”

Section: Factors That Might Set the Stage For Asthma Developmentmentioning

confidence: 99%

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The case of drug causation of childhood asthma: antibiotics and paracetamol

Heintze

Petersen

2013

Eur J Clin Pharmacol

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AimThe rising prevalence of bronchial asthma has led to world-wide efforts to understand and stem this development. Cross-sectional studies appear to show that early childhood use of antibiotics may be an important contributory factor, with paracetamol as an additional suspected cause. However, mounting evidence, which is reviewed here, points to various confounding factors as the major reasons for these reported associations.MethodsPubMed and EMBASE were systematically searched for studies on associations between antibiotics and/or paracetamol with asthma and/or wheezing, published up to November 2012. A total of 64 pertinent studies were identified, 35 focusing on antibiotics, 19 on paracetamol, and ten addressing both antibiotics and paracetamol, bringing the number of relevant datasets to 74.ResultsNumerous studies were cross-sectional and made no adjustment for the indication of antibiotics or paracetamol; consequently, they were unable to dismiss possible confounding by indication. Where such adjustments could be performed (mostly in longitudinal studies), they substantially weakened or entirely eliminated the association with asthma or asthma surrogates present in the unadjusted data.ConclusionThe weight of evidence of the collected studies in our review strongly suggests that the association of antibiotics with childhood asthma reflects various forms of bias, the most prominent of which is confounding by indication. Recent studies and meta-analyses support the same conclusion for paracetamol. Truly indicated antibiotics should not be withheld from infants or young children for fears they might develop asthma. Likewise, there is no sound reason to replace paracetamol as the preferred pain relief and fever medication in this age group.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-012-1463-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Factors That Might Set the Stage For Asthma Developmentmentioning

confidence: 99%

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The case of drug causation of childhood asthma: antibiotics and paracetamol

Heintze

Petersen

2013

Eur J Clin Pharmacol

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“…15 studies were excluded for the following reasons: antibiotic exposure was collected retrospectively (n54) [9][10][11][12]; no report on wheeze and/or asthma, but other allergic outcomes only (n56) [13][14][15][16][17][18]; no association measure for wheeze or asthma separately but an overall outcome called ''atopy'' which also included eczema and/or hay fever (n51) [19]; only prenatal antibiotic use reported (n53) [20][21][22]; and adult population (n51) [23].…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

“…Therefore, this study will only be discussed in the following section, together with the remaining eight studies in which the positive association could not be explained by RC. [29] FOLIAKI [24] Ecological design SARIACHVILI [17] JOHNSON [16] VOOR [18] BREMNER [13] BREMNER [14] EGGESBO [15] FAROOQI [19] MITCHELL [10] THOMSEN [11] AWASTHI [9] WJST [12] JEDRYCHOWSKI [21] McKEEVER [22] BENN [20] CULLINAN [23] FIGURE 1. Results of the literature search and selection of studies.…”

Section: Reverse Causationmentioning

confidence: 99%

Infant antibiotic use and wheeze and asthma risk: a systematic review and meta-analysis

Penders¹,

Kummeling²,

Thijs³

2011

Eur Respir J

130

108

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Our aim was to systematically review and meta-analyse longitudinal studies on antibiotic use and subsequent development of wheeze and/or asthma with regards to study quality, outcome measurement, reverse causation (RC; wheezing/asthma symptoms have caused prescription of antibiotics) and confounding by indication (CbI; respiratory tract infections leading to antibiotic use may be the underlying cause triggering asthma symptom development).English-language papers and studies published before November 1, 2010 with longitudinal observational design were included. Study quality was assessed using the Newcastle-Ottawa scale.We identified 21 longitudinal studies. The effect of antibiotic use on wheeze/asthma risk varied between studies. 18 studies were eligible for meta-analysis showing pooled OR 1.27 (95% CI 1.12-1.43) for wheeze/asthma. When we eliminated studies with possible RC and CbI, the pooled risk estimate in the nine remaining studies was attenuated to OR 1.12 (95% CI 0.98-1.26). Definition of wheeze/asthma and age at follow-up differed between studies. Three studies focused on wheeze/ asthma beyond 5-6 yrs of age with the presence of active symptoms and/or medication (pooled OR 1.08, 95% CI 0.93-1.23; dominated by one study).RC and CbI lead to overestimation of the association between antibiotic use and subsequent development of wheeze/asthma. Association was weak when fully adjusted for these types of bias. Heterogeneity of disease definition between studies could affect the results.

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Neutrophilic airway inflammation and association with bacterial lipopolysaccharide in children with asthma and wheezing

Hauk

Krawiec

Murphy

et al. 2008

Pediatric Pulmonology

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Asthma is a leading chronic childhood illness in the US. To gain further insight into the pathophysiology of childhood asthma, we studied markers of airway inflammation and possible triggers such as bacterial lipopolysaccharide (LPS) in 18 children with chronic asthma and persistent wheezing who underwent clinically indicated bronchoscopy and bronchoalveolar lavage (BAL). We predominantly found neutrophilic airway inflammation associated with increased levels of IL-8, metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP-1) and MMP-9/TIMP-1 ratio. A significant correlation was found between levels of LPS in BAL and airway neutrophils in BAL from a subgroup of children who had a tendency of increased levels of MMP-9 and TIMP-1, suggesting that increased LPS levels in BAL may contribute to chronic airway inflammation and early remodeling. Our data highlight the importance of defining chronic triggers of early airway inflammation in children and characterizing their inflammation, considering the use of bronchoscopy and BAL. Increased knowledge of airway inflammation in children may help prevent a more severe asthma phenotype and lead to environmental control measures and new treatment strategies to intervene against the establishment of irreversible inflammation.

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Risk factors for asthma at 3.5 and 7 years of age

Cited by 17 publications

References 52 publications

The case of drug causation of childhood asthma: antibiotics and paracetamol

The case of drug causation of childhood asthma: antibiotics and paracetamol

Infant antibiotic use and wheeze and asthma risk: a systematic review and meta-analysis

Neutrophilic airway inflammation and association with bacterial lipopolysaccharide in children with asthma and wheezing

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