Published Online: December 2, 2013
Previously Jay A. Nadel, MD, and others have described reversible loss of lung elastic recoil in acute asthma and Arthur F. Gelb, MD, and others noted persistent loss of lung elasticity in moderate-to-severe chronic asthmatics who never smoked. The loss of lung elastic recoil refers to the disruption of the normal lung parenchymal-airway integrity, such that there is physiologic loss of the driving pressure needed to forcibly exhale, and airways may collapse prematurely. These abnormalities are usually seen in emphysema as a result of lung tissue destruction due to chronic cigarette smoking or in rare cases due to an inherited protein alpha 1 antitrypsin deficiency.
In a Letter to the Editor in The Journal of Allergy and Clinical Immunology (JACI), Gelb and Nadel et al investigated the potential mechanism(s) responsible for loss of lung elastic recoil and expiratory airflow limitation in never smoked moderate-to severe asthmatics. They theorized that unsuspected lung tissue breakdown was responsible for loss of lung elastic recoil. For 5-22 years they prospectively studied 10 adult chronic asthmatics who never smoked, with persistent moderate-to-severe expiratory obstruction and no evidence for the inherited form of emphysema. None had exposure to known agents that cause lung injury. Therapy included inhaled corticosteroid (ICS), inhaled short and long acting beta2-agonist (LABA) and muscarinic antagonist, oral leukotriene receptor blocker, and tapering but not maintenance oral corticosteroid. Studies included lung function, high resolution-thin section (1 mm) lung CT at full inspiration. Three of 10 asthmatics who died unrelated to acute asthma, had autopsies with examination of formalin inflated lung. Control case included an 82 year old female chronic asthmatic on ICS + LABA who never smoked with normal lung function, and lung CT who died unrelated to asthma and was also autopsied.
The authors found abnormal expiratory airflow was equally related to both the loss of lung elasticity as well as to intrinsic small airway remodeling, compared to age matched normal controls. Examination of the lung CT and lung macroscopic sections revealed either trivial or very mild emphysema in the 3 asthmatics who were autopsied. However, microscopy revealed mild diffuse centrilobular emphysema, as well as typical asthma remodeling in large and small airways. Asthma control lung had insignificant lung tissue breakdown consistent with aging and no emphysema.
The authors concluded that clinically unsuspected microscopic mild, diffuse emphysema was a cause of both loss of lung elasticity and persistent expiratory airflow limitation in never smoked asthmatics. These observations have never been previously reported. Previously Thais Mauad MD et al noted emphysema limited only to the peribronchiolar area in fatal asthmatics. The current authors suspect the emphysema may be related to a pro-inflammatory response initiating a proteolytic cascade that leads to unsuspected lung tissue breakdown.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.