Peripheral airway involvement in asthma assessed by single-breath SF₆and He washout

Abstract

The aim of the study was to assess how deep into the acinar region the airway response to cold dry-air hyperventilation challenge (CACh) reaches in subjects with asthma of different severity.Peripheral airway function was measured using a single-breath sulphur hexafluoride (SF 6 ) and helium (He) washout test and overall airway function by forced expiratory volume in one second (FEV1) at rest, after CACh and b 2 -therapy in 55 adults with a history of asthma. The normalised phase-III slopes (Sn III ) for SF 6 and He were used to assess peripheral airway obstruction and the (SF 6 -He) Sn III difference to indicate where obstruction occurred. While a greater He versus SF 6 slope increase indicates a response close to the acinar entrance, the reverse indicates a response deeper into the acinar airspaces.Twelve subjects had a major fall in FEV1 (o20%) after CACh, 16 a minor fall (10-19%), and 27 did not react. Resting He and SF 6 Sn III were significantly greater in major responders with respect to minor and nonresponders, while resting FEV1 did not differ between the three groups. The major responders showed marked increases of He and SF 6 Sn III after CACh, with greater increase for He resulting in a negative (SF 6 -He) Sn III difference.To conclude, airways close to the acinar entrance participate in the overall airway response to cold-air challenge in asthmatic adults with marked airway hyperresponsiveness to cold, dry air. There is growing awareness that the inflammatory cell infiltration and airway wall thickening characteristic of bronchial asthma engage not only the large and the mediumsized airways but the entire airway tree [1][2][3]. The peripheral airways are usually defined as those airways with a diameter of v2 mm and correspond approximately to airway generations 8-23 of WEIBEL9S [4] model of lung architecture. Direct and indirect evidence of peripheral airway involvement in asthma have come from post mortem studies [5][6], tissue specimens obtained in vivo using bronchoscopic biopsy techniques [7], bronchoscopic airflow resistance studies in distal lung units [8][9][10], and inert-gas washout studies [11][12][13]. In a previous nitrogen (N 2 ) multiple-breath washout (MBW) study, STROM-BERG and GUSTAFSSON [13] assessed the peripheral airway effects of cold dry-air hyperventilation challenge (CACh) on asthma patients and controls [13]. After the challenge the asthmatic subjects demonstrated not only a fall in FEV1 but also increased overall ventilation inhomogeneity and gas trapping, indicating peripheral airway obstruction [14].Exercise-induced bronchoconstriction (EIB) is a common problem in children and adults with asthma [15,16]. The underlying mechanism of EIB is drying and cooling of the airways due to the increased ventilation necessary during physical exercise [17,18]. Evaporation of water from the thin airway surface liquid layer is thought to result in a hyperosmolar stimulus to inflammatory cells in the airway mucosa of asthmatic subjects and the subsequent production and release...

Airway closure on imaging relates to airway hyperresponsiveness and peripheral airway disease in asthma

“…This topographical construct is consistent with the known dysfunction of peripheral airways in asthma (5,8,15,17,18,41) and its association with AHR (5,8). Closure occurs both peripherally and centrally (8,10) and could be due to worse inflammation, edema, mucous production, surfactant abnormalities, airway wall thickening, and changes in wall compliance (19,40). By subjective assessment, airway closure occurs at the same location on different days (6).…”

Dual gas techniques for peripheral airway function: diffusing the issues

“…Even if lung geometry were to change dramatically so as to push the He and SF 6 diffusion fronts out of, or further into the acinus, similar principles would apply, with SF 6 representing more peripheral structures than He. The SF 6 -He phase III slope difference has been used as an indicator of peripheral lung disease: it has been correlated to histomorphometry of airways in the smoker's lungs [9], indicated peripheral changes in asthmatics [10], detected a specific peripheral response to methacholine in lung transplant recipients [11], and suggested peripheral sites of allergic reaction [12]. One pitfall when interpreting dual gas washout tests is that an absence of change in SF 6 -He phase III slope difference cannot exclude an intra-acinar effect, for instance when both proximal and peripheral acinar structures affect He and SF 6 phase III slopes to the same extent.…”

A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease

“…The second method for localising inhomogeneity is by analysing tidal or VC SBW-derived SIII that are simultaneously obtained from two inert gases of different diffusivity, e.g. SF 6 and He [12,28,29].…”