Peak expiratory flow variation measured at home:the role of environmental, clinical and genetic factors

Loohuis, A.M.M. (2013) Peak expiratory flow variation measured at home:the role of environmental, clinical and genetic factors. thesis, Medicine.

Text LoohuisAMM.pdf Restricted to Registered users only Download (1MB)

Abstract

Background: Asthma is a heterogeneous disease characterized by variable airflow obstruction and airway hyperresponsiveness. The precise mechanisms of development of the disease are still unclear. Peak expiratory flow (PEF) variability is considered to be a reflection of airway hyperresponsiveness and asthma control and is easily measured at home, yet it is unclear if genetic factors contribute to PEF variability. Objective: To study clinical- and environmental predictors of PEF variability within asthmatics, the correlation of PEF variability between members of asthma families and to determine the association of single nucleotide polymorphisms previously associated with lung function. Methods: Asthmatic adults (age: 41 yrs ±13) from two cohorts were studied to identify predictors (n= 499) and genetic associations (n=389). Intra familial correlation was analyzed within 167 asthma families (n= 808). PEF variability was expressed as amplitude of day (difference morning and evening) as percentage of mean, with 7 subsequent days of measurements. Results: Multivariate analysis showed that higher PEF variability was associated (p= 0.05-<0.001) with older age, higher number of blood eosinophils, current smoking, higher reversibility, more severe hyperresponsiveness to histamine, and measures of airway obstruction (lower Tiffeneau index, lower FEV1 and lower MEF75, MEF50 and MEF25). Second, within asthma families there is higher correlation of PEF variability among first-degree relatives (r= 0.127-0.118) compared to second- and third degree relatives (r= - 0.026 - 0.055). Intrafamilial correlation were higher in father – child pairs compared to mother – child pairs. Third, SNP rs2857595 upstream of the NCR3 gene, was significantly (p= 0.012) associated with PEF variability at home. Conclusions: These findings show PEF variability within asthmatics can be predicted by airway hyperresponsiveness and (reversibility of) airway obstruction, which reflects both the airway diameter as well as the response of the airway to bronchoconstricting or –dilating agents. Moreover, within asthmatics, PEF variability is associated with eosinophilia in blood, suggesting a role of eosinophilic airway inflammation. Finally, the only environmental factor that was shown to negatively affect PEF variabilitiy was cigarette smoking. Our family study strongly suggests that PEF variability clusters in families and may in part be regulated by genetic factors, such as NCR3, a gene previously implicated to affect FEV1 levels in the general population.

Item Type:	Thesis (Thesis)
Supervisor name:	Koppelman, Prof. Dr. G.H.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:01
Last Modified:	25 Jun 2020 11:01
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2096

Actions (login required)

View Item