Dysfunction of Pulmonary Surfactant in Asthmatics after Segmental Allergen Challenge

Abstract

Increased airway resistance in asthma may be partly due to poor function of pulmonary surfactant. This study investigated the inflammatory changes of bronchoalveolar lavage fluid (BALF) and the performance of BALF surfactant in healthy control subjects (n = 9) and patients with mild allergic asthma (n = 15) before and after segmental challenge. BALF was obtained for baseline values, and 24 h after challenge with saline solution in one lung segment and with allergen in another. Cell counts, phospholipid and protein concentrations, and ratios of small to large surfactant aggregates (SA/LA) were analyzed. Surface tension was determined with a pulsating bubble surfactometer, and the ability of the BALF surfactant to maintain airway patency was assessed with a capillary surfactometer. Baseline values of control subjects and asthmatics were not different. Challenge with saline and antigen raised total inflammatory cells in both control subjects and asthmatics. Allergen challenge of asthmatics, but not of healthy volunteers, significantly increased eosinophils, proteins, SA/ LA, and surface tension at minimum bubble size, and diminished the time the capillary tube is open. In conclusion, allergen challenge in asthmatics induced surfactant dysfunction, probably mainly because of inhibiting proteins. During an asthma attack, narrow conducting airways may become blocked, which might contribute to an increased airway resistance.

Surfactant function affected by airway inflammation and cooling: possible impact on exercise-induced asthma

“…Bovine albumin and fibrinogen were purchased from Sigma, St. Louis, MO, USA. Albumin was dissolved in saline solution and when mixed with the CLSE suspension its final concentrations became 5,6,7,8,9, and 10 mg . mL -1 .…”

“…The cell free fluid was then centrifuged at 40,0003g and 48C for 1 h to obtain a pellet of surfactant. The supernatant we knew from a previous study [5] contained water soluble surfactant inhibitors when the fluid originated from allergen challenged segments of asthmatics. To increase the inhibitor concentration, the supernatant was evaporated until its volume had been reduced to a fifth, and it was then used for a dilution of CLSE from 35 to 1 mg .…”

“…It has been demonstrated that the inflammation caused by exposure to ozone [1,2] or by an infection with respiratory syncytial virus (RSV) [3,4] inactivates the surfactant system and leads to disturbed breathing. More recently it has been shown [5,6] that the inflammation developing in patients with mild asthma who have been challenged with an allergen causes surfactant to lose its ability to maintain patency. Most likely the inability was due to a leakage of plasma proteins into the airway lumen since it was noted that protein concentration in the lavage fluid was increased.…”

“…Those features of asthma may be caused by ozone exposure [10] or by RSV infection [11], conditions that both trigger an inflammatory reaction. Since it has now been established that in mild asthmatics an allergen challenge inducing an inflammatory reaction will provoke a surfactant dysfunction [5,6], it appears very likely that the increase in airway resistance characterizing an asthma attack is partly due to a surfactant dysfunction. Since an asthma attack will often be triggered in asthmatics exercising and therefore hyperventilating in cold weather, it appears logical to evaluate surfactant's ability to maintain patency at temperatures below those of the body.…”

Lung Surfactant and Its Use in Lung Diseases

“…Дефицит и/или качественные изменения состава ЛС опи саны при РДС новорожденных [2], синдроме острого повреж дения легких (СОПЛ) и остром респираторном дистресс син дроме (ОРДС) [6][7][8], пневмонии [9][10][11][12], кистофиброзе поджелудочной железы [13,14], идиопатическом фиброзирую щем альвеолите [15,16], ателектазах [17], лучевом поврежде нии легких [18], бронхиальной астме [19][20][21][22][23][24][25], хронических об структивных болезнях легких (ХОБЛ) [26], саркоидозе [27], туберкулезе [28,29] и других заболеваниях [26].…”