Peripheral airway function in asthma and cystic fibrosis. Measurements using inert gas washout methods

Abstract: It is increasingly recognised that asthma and cystic fibrosis (CF) frequently involves the peripheral airways. Characteristic features of abnormal peripheral airway function are uneven ventilation distribution and increased gas trapping. The overall purpose of the work presented in this thesis was to set up methods based on washout of inert gases, and use them to assess peripheral airway engagement in infants, children and adults with asthma or CF.An SF6 multiple-breath washout (MBW) technique and a modified SF6 and He single-breath washout (SBW) method were used to study peripheral airway involvement in asthma and CF. The feasibility of measuring trapped gas using the MBW technique in conjunction with passive lung inflations in infants was investigated. The volume of trapped gas in infants with CF and controls was assessed by comparing functional residual capacity as measured by MBW and by plethysmography. Subjects with CF and controls underwent MBW and the SF6/He SBW test, and new analytical approaches to analysis were used to determine contributions to ventilation inhomogeneity from the conductive and the intra-acinar airways. Adults with a history of asthma and hyperreactive asthmatic children were studied using SF6/He SBW tests at rest, after challenge and again after bronchodilator therapy to investigate involvement of airways in the acinar region.Both gas trapping and uneven ventilation distribution could be measured with good precision in infants using the MBW in combination with plethysmography or with the MBW technique only. Infants with CF had significant gas trapping when compared to control infants, who, contrary to previous findings, did not have significant amounts of trapped gas. Asthmatic children and adults who reacted with marked airway obstruction to airway challenge showed increased overall ventilation inhomogeneity, and findings suggested that airways as far peripherally as close to the acinar entrance participated in this overall airway response. In addition, there was evidence that structural or functional peripheral airway abnormalities at rest are important determinants of the severity of the response to challenge. Patients with CF had marked inhomogeneity of overall ventilation distribution as measured by the MBW and SBW tests. Abnormal ventilation distribution was found in both the conductive and the intra-acinar airways, and there was evidence that abnormalities extended at least into the proximal portion of the acinus.Summary and conclusion: Peripheral airway involvement can be assessed in a patient-friendly manner in infants, children and adults with airway disease using the MBW. New analytical approaches to analysis of the MBW and the SBW in subjects with CF and asthma demonstrate that both conditions commonly involve the peripheral airways, at least as far as the proximal portion of the acinus. Peripheral airway involvement is generally more pronounced in children with CF than in those with asthma and appears to be related to clinical disease severity. The methods described may prove valuable when evaluating treatments targeted at the peripheral airways.