Published Online: September 1, 2014
Aspirin Exacerbated Respiratory Disease (AERD) is clinically characterized by the triad of asthma, nasal polyps, and intolerance to cyclooxygenase (COX)-1 inhibitors such as aspirin. Although overrepresented in severe asthma, AERD can be difficult to identify and therefore likely under-diagnosed, partly because most patients use COX-1 inhibitors infrequently, or may not link worsened asthma control with ingestion of these drugs. Since a pathognomonic biomarker has yet to be identified for AERD, descriptors that distinguish this asthma subtype are invaluable clinical tools. Although anecdotal and limited data suggested a greater prevalence of alcohol-induced respiratory reactions in AERD than in other asthma types, a study recently published in The Journal of Allergy and Clinical Immunology: In Practice has more fully defined the prevalence and characteristics of alcohol-induced respiratory symptoms in patients with AERD. Using a questionnaire study design, Cardet and colleagues found that patients with AERD had remarkably higher rates of alcoholic beverage-induced respiratory reactions compared to aspirin-tolerant controls.
This was a cross-sectional survey study where a questionnaire assessing alcoholic beverage-induced respiratory symptoms was administered to patients from the Brigham and Women’s Hospital or Scripps Clinic. Study participants were recruited into four clinical groups consisting of: 1) patients with aspirin challenge-confirmed AERD, 2) aspirin-tolerant asthmatics (ATA), 3) aspirin-tolerant patients with chronic rhinosinusitis (CRS), and 4) healthy controls. A history of respiratory reactions to alcohol was evaluated and classified into ‘upper reactions’ (if participants affirmed developing either “stuffy nose/nasal congestion”, or “runny nose”) or into ‘lower reactions’ (if they affirmed developing either “shortness of breath” or “wheezing”). Data were also collected characterizing these reactions with regards to time to onset, frequency, specificity to alcohol type, quantity of alcohol required to provoke reactions, whether they had cut down their alcohol consumption due to the development of respiratory reactions, and for subjects with AERD who had been desensitized to and continued treatment with daily high-dose aspirin, whether aspirin therapy blunted alcohol-induced reactions.
The majority of patients with AERD reported experiencing alcohol-induced respiratory reactions. 83% of participants with AERD developed alcohol-induced respiratory symptoms, in contrast to 43% of ATA controls, 30% of patients with CRS, and 14% of healthy controls, with lower (and therefore, more severe) respiratory reactions reported 2.5 times as often by participants with AERD than by participants with ATA. Of the participants reporting respiratory reactions, many identified red wine as the most forceful trigger, but no single alcohol type was determined to be the main culprit. More than 1/3 of asthmatic participants with either AERD or ATA reported that all alcohol types were equivalent triggers for respiratory reactions. Almost all participants with AERD or ATA reported needing fewer than three glasses of alcohol for their reactions to happen, and for the majority these reactions happened within one hour of ingestion. For most participants with either AERD or ATA, these reactions happen “more than half” or “all the time” that they consume alcoholic beverages. Of the participants with AERD who had undergone aspirin desensitization and were maintained on daily high-dose aspirin therapy, 63% reported an amelioration in their reactions to alcoholic beverages since starting such therapy. Finally, in participants with AERD the severity of aspirin-induced reactions correlated with the severity of alcoholic beverage-induced respiratory reactions.
The study by Cardet et al investigated the prevalence and characteristics of alcohol-induced reactions in well-phenotyped patients with AERD and in aspirin-tolerant controls. Based on its results, a history of alcoholic beverage-induced respiratory reactions may increase the suspicion for the diagnosis of AERD and clinicians should warn their patients with known AERD about the possibility of alcohol-induced symptoms.
In response to this study by Cardet and colleagues, Spencer Payne lays out a theory regarding the mechanisms of these reactions in correspondence published in a recent issue of The Journal of Allergy and Clinical Immunology: In Practice. Payne proposes that the source of the problem may not be the alcohol itself, but other ingredients commonly found in the beverages. Aspirin, ibuprofen, naproxen and other NSAIDS help stop pain and fever because they block an enzyme called cyclooxygenase that is critical in creating other chemicals that cause inflammation. Unfortunately, in patients with AERD, blocking this enzyme makes their sinus and asthma symptoms worse for a variety of reasons. In addition to aspirin, a group of naturally occurring substances found in plants known as polyphenols can also block cyclo-oxygenase. Polyphenols are frequently found in red wine, where they come from the grape skin, and in beer, where they come from the barley and hops added to the brew. In the case of white wine and liquor, one can expect the presence of polyphenols derived from the oak barrels in which they may be aged.
Research is currently underway to explore this concept, and if confirmed, will help clinicians counsel their patients with AERD as to which alcoholic beverages may be safe to consume (in theory steel fermented white wines and clear liquors) so they can continue to enjoy an activity that often forms the basis of many of our social events and celebrations.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.