Previous studies indicate that unexplained chronic cough—persistent cough with no identifiable cause after investigation and therapeutic trials—occurs in up to 10% of patients seeking medical assistance for chronic cough. “Although cough is just a symptom, it’s a sign of something that can be serious,” says Kenneth W. Altman, MD, PhD, FACS. “Determining the cause can be challenging because an entire spectrum of factors could play a role, ranging from cancer to neurologic causes to smoking.”

With the National Ambulatory Medical Survey indicating that 3% of physician office visits in 2005 were for cough and physicians seeing about 1 billion patients each year in the United States, Dr. Altman says the economic impact of cough is significant. “Beyond its high prevalence and burden on the healthcare system,” he says, “the potential seriousness of the disease causing the underlying cough is the most important reason why addressing unexplained chronic cough needs to be better understood and treated.”


A Systematic Review

Dr. Altman and a group of experts from the American College of Chest Physicians (ACCP) published a guideline and expert panel report in CHEST on the treatment of unexplained chronic cough. The team first conducted a systematic review of randomized controlled trials among patients older than 12 years with a chronic cough that was unexplained after systematic investigation and treatment and lasted longer than 8 weeks. “We found that the highest-quality trials didn’t have uniform criteria for defining unexplained chronic cough,” says Dr. Altman. “Diagnostic workup, descriptors, and assessments to identify unexplained chronic cough varied among studies. The takeaway message here is that standardization of our approaches to patients with chronic cough is important to optimizing outcomes.”

Among the 11 trials included in the systematic review, 570 participants with chronic cough received a variety of interventions. Whereas cough-related quality of life improved with gabapentin and morphine, only gabapentin was supported as a treatment recommendation. When researchers accounted for intervention fidelity bias in studies involving inhaled corticosteroids, these agents were found to be ineffective against unexplained chronic cough. When unexplained chronic cough was unrelated to GERD, esomeprazole was found to be ineffective. However, cough severity was improved when clinicians intervened with a multimodality speech pathology intervention.


Suggestions & Recommendations

Based on data from the systematic review, Dr. Altman and colleagues developed six overriding recommendations and suggestions (Table). “Clinicians should consider cough to be chronic if it lasts longer than 8 weeks,” says Dr. Altman. “Cough can be considered ‘unexplained’ if different medications targeting the clinically suspicious causes are ineffective after conducting an objective workup and testing.”

Dr. Altman says that a standard decision-making process for managing complex patients will most often provide the best outcomes. “We also recognize that behavioral interventions—suppressing cough when the urge arises and avoiding triggers—with speech therapy can effectively improve quality of life in patients with chronic cough,” he adds. 

According to the guideline, objective testing should be performed to rule out cough-variant asthma or eosinophilic allergic or non-allergic inflammation in the lungs. If patients have neither of these conditions, then medication should not be prescribed to treat these health issues.

The research by Dr. Altman and colleagues also examined studies on numerous medications that can be used to suppress cough. “The medication with the highest level of proof that it is effective for treating unexplained chronic cough was gabapentin,” explains Dr. Atlman. “Gabapentin suppresses the cough reflex by elevating the cough threshold, but it also has some side effects that must be considered.”

Clinical studies have shown that acid reflux can also contribute to cough, but Dr. Altman says that clinicians should avoid prescribing a medication for acid reflex if there is no symptomatic or objective testing evidence for reflux.


Important Implications

According to Dr. Altman, it is important for clinicians to recognize that ACCP guidelines have, for more than 15 years, recommended chest x-ray and discontinuing ACE inhibitors for all patients with chronic cough, except in rare circumstances. “It’s also important to recognize that a cough is a sign of something potentially serious,” he says. “If it has lasted longer than 8 weeks, it should definitely be evaluated. Clinicians should use a protocolized approach and be systematic with an empiric trial of a targeted medicine.”

If these strategies are ineffective, Dr. Altman recommends using objective testing to better understand the problem. “The key is determine if the cough is due to allergy, sinus, pulmonary, or reflux-related causes or if there is another unidentified cause,” he says. “The role for medical or behavioral therapy to suppress the cough and improve patients’ quality of life should also be considered.”