ATLANTA (FRONTLINE MEDICAL NEWS) – Asthma exacerbations are common, severe events that can be life-threatening and can accelerate loss of lung function. That’s why it’s important to flag high-risk patients in your clinical practice, Nizar N. Jarjour, MD, said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Each year in the United States there are 15 million clinic visits, 2 million ED visits, and 500,000 hospitalizations for severe asthma exacerbations. “These exacerbations cause a high cost on the health care system, they lead to loss of work or school, and they’re a burden to patients and certainly to their families,” said Dr. Jarjour, professor of medicine and division head of allergy, pulmonary and critical care at the University of Wisconsin, Madison.

Factors implicated in asthma exacerbation include air pollution, cigarette smoke, occupational exposure, stress, and allergen exposure, but 50%-85% of cases are related to viral upper respiratory infections. “Any respiratory pathogen can precipitate attacks, but rhinoviruses are the most common,” he said. “Seasonal viral [upper respiratory infections] correlate with hospital admissions for asthma, and peak in spring and fall.”

Purported ways that a viral upper respiratory infection can lead to asthma exacerbation include enhanced airway responsiveness, increased eosinophilic airway inflammation in response to antigen, enhanced lower airway neutrophilic inflammation, and direct infection of the lower airway. “There are is an accentuated eosinophilic inflammation in response to allergen challenge when somebody has a cold,” Dr. Jarjour explained. “But the viral infection can actually directly lead to eosinophilic inflammation, perhaps through TSLP [thymic stromal lymphopoietin], interleukin (IL)-25, and IL-33 simulating the ILC2 (type 2 innate lymphoid cells). So there are both accentuating response to allergens as well as direct enhancement of eosinophilic inflammation following viral infection.”

One study that examined airway lavage following experimental infection found that patients had increased numbers of neutrophils in their airway sample ( J Allergy Clin Immunol. 2000;105:1169-77 ). This means that asthma exacerbation triggers neutrophilic inflammation, which relates to the induction of cytokines and chemokines in the upper airway. “We have also demonstrated increased circulation of G-CSF [granulocyte–colony stimulating factor] and nasal IL-8 in the upper airway related to increased neutrophil recruitment,” Dr. Jarjour said.

Host factors associated with asthma exacerbations include altered innate immune response in the form of a defect in production of antiviral cytokines in response to viral infection, and a greater T helper (Th)2/Th1 ratio. Other factors include eosinophilic inflammation and greater levels of specific IgE to dust mite. Baseline data from 709 patients enrolled in the National Heart, Lung, and Blood Institute Severe Asthma Research Program III (SARP-3) showed that three top risk factors for asthma exacerbations are gastroesophageal reflux disease (relative risk (RR) 1.6), greater blood eosinophil count (RR 1.6), and obesity (RR 1.2) ( Am J Resp Care Med. 2017; 195:302-13 ).

Risk factors for exacerbation noted in various epidemiological studies include African American and Hispanic races, poor access to medical care, inadequate chronic control, smoking, allergen sensitivity to cats and dogs, gastroesophageal reflux disease, high body mass index, sinusitis, and uncontrolled eosinophilic inflammation. Key findings from a follow-up study of SARP-3 patients include the fact that the absence of exacerbations on a 12-month recall predicted future stability.

“More importantly, participants with severe disease and two or more exacerbations at baseline had a 75% chance of having an exacerbation in the following year,” Dr. Jarjour said. “This is a call for us to pay more close attention to these patients and is an important fact to keep in mind when designing clinical trials. A history of exacerbations is the best predictor of future exacerbation.”

Dr. Jarjour disclosed that he has received research funding from the National Heart, Lung, and Blood Institute and consulting fees from AstraZeneca and Teva Pharmaceutical. He is a member of the American Board of Internal Medicine–Pulmonary Exam Subcommittee.