Airway smooth muscle: an architect of the lung?

Abstract

This review examines the rationale for increased study of the prenatal development of airway smooth muscle (ASM). With a critical role in asthma and airway remodelling, ASM has been extensively investigated. Nevertheless, there is a paucity of studies looking at prenatal ASM development and function. A working party report from the National Heart Lung and Blood Institute identified this issue and has recommended further investigation. The impetus for this call stems not only from an appreciation that childhood and adulthood disease may have their origins in fetal life, but also because recent studies indicate that prenatal ASM regulates lung development (via its phasic contractility and growth factor production). Moreover, recognition that phasic ASM contractility is the prenatal norm has raised interest in the idea that postnatal reactive airways disease may likewise be a periodic oscillatory phenomenon. Finally, bronchial thermoplasty represents an exciting new therapy for refractory asthma. However, the mechanism for its effects is unclear. Recent studies show that prenatal ASM contractility is governed by a hierarchy of pacemakers within proximal airways. If such a pacemaker arrangement persists postnatally, it is possible that bronchial thermoplasty achieves its distal airway effects via ablation of controlling proximal pacemaker centres. Hence, study of prenatal ASM may allow us not only to develop ways to stimulate prenatal lung growth, but also to understand and develop new therapies for reactive airways disease.

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

“…One relevant issue during fetal development is the role of mechanical stretch and the concept of airway peristalsis (134,135) and cyclical Ca 2ϩ waves within fetal ASM cells that can promote airway branching and elongation. Such spontaneous peristaltic Ca 2ϩ waves and contractions appear to be coupled and arise from specific "pacemaker"-like ASM cells and intercellular communications via gap junctions (71,136).…”

Dimethylfumarate inhibits CXCL10 via haem oxygenase-1 in airway smooth muscle

“…The pathological increase of ASMC number and size in asthmatic airways was first reported by HUBER and KESSLER [15] in 1926 and this finding was later confirmed to occur in childhood asthma, often before any sign of inflammation is detected [16,17]. In asthma, ASMCs constrict and narrow the airways upon exposure to a wide range of triggers, thereby limiting airflow.…”

“…ASMCs were grown in RPMI-1640 (ThermoTrace, Melbourne, Australia) supplemented with 5% (v/v) heat-inactivated fetal bovine serum (FBS), 16 Minimal Essential Medium vitamin mix, 100 U?L -1 penicillin, 100 mg?mL -1 streptomycin, 0.25 mg?mL -1 amphotericin B (all GIBCO/BRL, Melbourne, Australia), 25 mM hydroxyethyl piperazine ethane sulfonic acid and 2 mM L-glutamine (both ThermoTrace) in a humidified 5% carbon dioxide atmosphere at 37uC. ASMCs were used between passages 5 and 8.…”

Bronchial thermoplasty; a new treatment modality in asthma

“…Astım patogenezinde önemli bileşenlerden birinin küçük hava yolları olduğu düşünüldüğünde bronşiyal termoplastinin 3 mm üzerindeki lober ve segmental bronşlara uygulanmasıyla klinik iyileşme sağlanması patogenezin ne kadar karmaşık olduğunu ve proksimal hava yollarının da patogeneze katıldığını göstermektedir. Jesudason ve arkadaşları hava yolu düz kas kontraktilitesinin proksimal hava yollarında bulunan bir pacemaker tarafından düzenlendiğini ve bronşiyal termoplastinin bu merkezde ablasyon yaparak distal hava yollarında etkili olduğunu öne sürmüşlerse de büyük hava yolları inflamasyonu komponentinin ön planda olduğu astım fenotiplerinde daha etkili oluyor olabileceği de göz önünde tutulmalıdır (17).…”