Constrictive bronchiolitis should be considered in all returning veterans who report exercise limitations due to dyspnea, according to the authors of a report in the July 21 issue of the New England Journal of Medicine.

Lung biopsies revealed diffuse constrictive bronchiolitis in 38 of 49 previously healthy soldiers who developed unexplained exertional dyspnea and diminished exercise tolerance after serving in Iraq or Afghanistan, said Dr. Matthew S. King of the division of pulmonary and critical care medicine, Meharry Medical College, Nashville, Tenn., and his associates (N. Engl. J. Med. 2011;365:222-30).

Although most of the 38 soldiers had been exposed to smoke from a sulfur-mine fire in northern Iraq, 10 reported no potentially toxic exposures – a "particular concern" given that the potential toxic exposures among those 10 may be similar to those of most troops who were deployed to Iraq and Afghanistan.

The rare disorder is a challenge to diagnose, especially in the absence of known predisposing conditions such as rheumatologic disorders, because patients often show low-normal pulmonary function and normal radiologic results.

During a recent 5-year period, the investigators evaluated 80 soldiers from one Kentucky military base who had persistent respiratory symptoms and exercise intolerance – an extensive assessment that included a detailed review of occupational and environmental exposures. A total of 49 were referred for video-assisted thorascopic lung biopsy by their treating physicians.

Of those 49, 38 were found to have diffuse constrictive bronchiolitis. The 35 men and 3 women had a median age of 33 years (range, 23 years to 44 years), and had served in a variety of positions. All had met the requirements of U.S. Army readiness testing wearing full combat gear before being deployed, but now became breathless after climbing a single flight of stairs.

Chest radiography had yielded normal findings in 37 of the soldiers, and high-resolution CT had done so in 25 soldiers. "Only a few soldiers had high-resolution CT showing the centrilobular nodules or expiratory air trapping that can be associated with constrictive bronchiolitis," the researchers said.

Spirometry results, lung volumes, and measures of carbon monoxide diffusing capacity had been normal in 13 of the soldiers, while another 19 had shown only isolated low carbon monoxide diffusing capacity.

All of the 30 soldiers who had undergone cardiopulmonary exercise testing showed mean levels of maximal oxygen consumption and an anaerobic threshold that were in the low-normal range. However, when compared with results for military control subjects rather than controls from the general population, their mean maximal oxygen consumption was significantly lower, and their anaerobic threshold was significantly reduced.

During biopsy, 37 of the 38 soldiers were found to have lacy black pigment on the visceral pleural surface, and specimens demonstrated polarizable material within the pigment. That is consistent with inhalation of particulate matter.

The biopsy specimens also showed mixed airway-wall inflammation and membranous bronchioles containing hypertrophic mural smooth muscle or fibrous thickening that narrowed the lumen in the small airways. That finding, too, is consistent with toxic inhalation.

Culturing the biopsy samples yielded negative results on all attempts to identify bacteria, fungus, or acid-fast bacilli, Dr. King and his colleagues said.

Of the 38 soldiers, 28 had been exposed to smoke from a sulfur-mine fire in northern Iraq, 33 had been exposed to dust storms, 24 to incinerated solid waste in large burn pits, and 18 to incinerated human waste. However, 10 solders reported no potentially toxic exposures at all.

"We expected that the finding of constrictive bronchiolitis would be limited to" the soldiers with prolonged exposure to toxic levels of sulfur dioxide from the sulfur-mine fire, the researchers explained. But soldiers without such exposure also developed the disorder.

"This group causes particular concern, since their potential toxic exposures are shared by most personnel who were deployed to Iraq and Afghanistan," the investigators noted. "These common exposures include open-air burn pits, in which solid waste was routinely incinerated in close proximity to living quarters, and desert dust storms of such severity that they obscured visibility.

"The presenting symptoms, smoking histories, evaluations, and biopsy samples of the 10 soldiers who did not report exposure to the sulfur-mine fire were indistinguishable from those of the 28 soldiers who did report such exposure," the researchers added.

Twenty-seven of the 38 soldiers responded to a follow-up survey in 2010. Nineteen had left the military with a "disabled" rating, while 8 were still serving "despite their inability to complete a 2-mile run within the regulation time." Twenty-two reported that their respiratory problems limited their job opportunities.

Since the case series was completed, nine more soldiers who presented to Dr. King and his associates have been diagnosed as having constrictive bronchiolitis, they noted.

The study was supported in part by the National Center for Research Resources. One of Dr. King’s associates reported ties to Actelion Pharmaceuticals.

U.S. Soldiers May Return With Constrictive Bronchiolitis