Asthma Exacerbation: “Sneaky” Triggers and Clinical Pearls
- Jan 7th, 2019
- Adam Rodrigues
Authors: Adam Rodrigues, MD (Lincoln Medical Center Bronx, New York); Joel Gernsheimer, MD (SUNY Downstate Medical Center, New York); Muhammad Waseem, MD, MS (Lincoln Medical Center Bronx, New York; St. Georges University Grenada West Indies) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)
A 22-year-old female presents to the ED with shortness of breath and wheezing since this morning. She states she has a history of asthma and this feels like her usual symptoms. She’s been intubated once before as a child but states today’s exacerbation doesn’t feel quite as bad. She has been hospitalized three times with asthma, most recently a year ago. She is a nonsmoker. She denies recent travel, immobilization, calf tenderness, leg swelling, bruising, oral contraceptive use, or a history of blood clots.
Vital signs show temperature of 98.7, pulse 98, BP 132/78, RR 21, SpO2 97% on room air. Lung exam reveals mild to moderate diffuse expiratory wheezing. Her initial peak flow is 250 L/min, and she states her best is 520 L/min.
What additional questions do you have for her? What are your next actions?
A morbidly obese 34-year-old woman with a history of hypertension is brought to the ED by EMS with complaint of shortness of breath and altered mental status. The patient is on a CPAP mask, which she is actively trying to remove. She is agitated and confused. The primary survey reveals that her airway is open, she has decreased breath sounds bilaterally with diffuse wheezing, strong rapid radial pulses, GCS of 14, and no evidence of trauma. Her finger stick glucose is 145 mg/dL. EMS states family at the scene indicated she has a history of asthma. Vital signs are temperature 99.0, pulse 135 BPM, BP 172/99, RR 29, SpO2 91% on the EMS CPAP mask.
What are your next actions? What are other questions about her history you should ask?
Background and Introduction
Asthma affects 8% of the US population with 9% prevalence in children.  It has a similar prevalence in other developed nations. It’s characterized by an abnormal inflammatory response involving multiple immune cell types that causes a reduction in airway diameter by smooth muscle contraction, vascular congestion and edema, and secretions. 
It is well established that a variety of environmental and host factors contribute to the development of asthma.  Determining a link between the trigger of an episode of shortness of breath in a patient presenting to the ED with prior history of asthma can be key to ruling in asthma as the most likely diagnosis. Also, identifying the trigger of an acute exacerbation of the patient’s asthma may lead to treatment of the underlying cause of that exacerbation and help shorten the duration and decrease the severity of that acute attack. For example, treating an underlying pneumonia with antibiotics in a patient with an acute exacerbation of asthma will decrease the morbidity and mortality of that attack. Additionally, trigger identification is a key element in long-term asthma management, as eliminating these triggers will help obtain adequate symptom control, maintain normal activity levels and decrease the incidence and risk of exacerbations.  This article will briefly review some common asthma triggers, and then discuss the “sneaky,” often less recognized asthma triggers.
Common Asthma Triggers
Allergic asthma is believed to be triggered when pre-formed IgE binds to MAST cells, causing the release of inflammatory mediators and subsequent bronchoconstriction and airway narrowing characteristic of both asthma exacerbation and allergic rhinitis.  Allergic triggers can be further subcategorized into animal-type and pollen triggers, although different studies may individually separate, or group together, agents such as grass, ragweed, tree pollen, and fungal spores as either “allergic” or “air pollutant/inhalant.” 
Animals commonly implicated as triggers for exacerbation of asthma include domestic pets (cats and dogs) as well as those more commonly considered pests, such as mice and cockroaches as well as the Dermatophagoides species of dust mites.  Pollen is another common allergic trigger. An asthma questionnaire implicated dust, pollen, seasonal factors and smoking as some of the most common factors precipitating asthma exacerbations.  While pollen is often cited by patients as a significant contributor to their asthma, some studies show only about 35% of these patients demonstrate evidence of skin reactivity, which is as relatively small, but nonetheless significant association. 
Physical activity is a known precipitant of acute asthma exacerbation.  One study found physical activity was among the top asthma culprits as reported by up to 45.9% of respondents.  This is important as attacks of asthma may be aborted by educating these patients to use their rescue inhalers, such as albuterol, just prior to exercise.
Air Pollutants / “Inhalants”
Atmospheric pollutants not expressly falling into the “allergic” category, especially those specific to densely populated urban areas, are associated with higher incidence and severity of asthma exacerbation.  These may include tobacco, industrial chemicals, grass, ragweed, tree pollen, and fungal spores.  In Germany, 37.3% of perceived exacerbations were due to air pollution , and a study in Pakistan demonstrated similar results. 
URI’s are a common cause of asthma exacerbations in children, and some studies show that infectious triggers correlate with the most severe of asthma exacerbations.  Rhinovirus, RSV, and coronavirus have been shown to increase numbers of circulating neutrophils and eosinophils.  One study from Spain indicated that a slow-onset common cold accounted for up to 47% of acute asthma exacerbations.  Additionally, just as we now consider the gut microbiome to be implicated in our ability to digest food, one recent study centered around the nasopharyngeal biome of 234 infants. It was found that colonization by RSV and Human Rhinovirus plus strep coinfection at 2 months of age had a strong correlation with the development of asthma by age 5, and that antibiotic treatment reduced this risk.  However, while infections with atypical organisms, such as Chlamydia and Mycoplasma, increase the severity and duration of asthma exacerbations in adults, especially those with steroid resistant asthma,  a short course of antibiotics (e.g. three days of azithromycin) was not shown to increase lung function or speed of recovery, or to reduce symptoms over a 10-day period. 
Sneaky Asthma Triggers
GERD (gastroesophageal reflux disease) and LPR (laryngopharyngeal reflux) are two less commonly recognized triggers for asthma, but there is sufficient evidence to suggest at least some correlation between these two entities and asthma exacerbations. One review noted that 59% of asthmatics had symptoms consistent with GERD, such as heartburn, regurgitation, dysphagia, chest pain, hoarseness, dental erosions, and symptom worsening while supine.  This has spawned three proposed mechanisms underlying GERD-related bronchoconstriction: increased vagal tone, bronchial sensitization, and/or micro-aspiration of gastric contents into the upper airway.  Additionally, it has led some experts to offer asthmatics similar symptom control recommendations as those given to patients with reflux, such as sleeping with the head of the bed elevated, avoiding PO intake 2-3 hours before sleep, weight loss, and the avoidance of foods known to exacerbate GERD, such as fatty foods, peppermint, chocolate, and alcohol.  Also, if GERD or LPR are strongly suspected, the patient can be given a trial of a PPI to see if that relieves symptoms.  Although not a trigger for asthma, Paradoxical Vocal Fold Dysfunction may mimic a severe asthma exacerbation, and even lead to the patient being intubated. However, pulmonary function is normal, as the pathology is caused not by a lung problem, but by abnormal closure of the vocal cords during inspiration, and these patients will complain of trouble during inspiration, not on expiration, as occurs in asthma. 
Beta blockers have traditionally been avoided over concern for their ability to adversely provoke acute asthma exacerbations. More recent evidence indicates that β1-selective β-blockers may cause an average decrease in FEV1of 6.9%, and are capable of causing a dose-dependent decrease in FEV1of up to 20% when compared with placebo. However, such patients were not at statistically significant risk of increase in symptoms.  Additionally, nonselective β-blockade caused an average decreased in FEV1of 10.2% and an increase in symptoms in a small but statistically significant cohort. 
For those asthmatics on angiotensin converting enzyme inhibitors (ACEI) therapy, a continuous or persistent cough, which can be an adverse effect of these medications, may be confused with an acute exacerbation of their asthma.  Also, some asthmatics have asthma that is exacerbated by aspirin and NSAIDS, and asthmatic patients should always be questioned about possible sensitivity to these medications before being given aspirin or other NSAIDS. 
A number of reviewed studies have evaluated asthma triggers as understood and interpreted by patients’ experiences. These studies generally do not consist of systematic, controlled exposures to varying levels of noxious antigens. Many papers have sought to elucidate the significant psychological components underlying asthma exacerbations. Consider that from the perspective of a patient, “An asthmatic perceiving a trigger, or the cue for it, such as an odor, as potentially harmful may initiate cognitive and emotional processes, leading to the interpretation of an uncontrollable health threat” and that in this way, repeated exposure to a particular trigger may signify a learning process that pairs that trigger with “symptom experiences, and finally, central sensitization.”  Additionally, emotional stress and depression are known to affect asthma control, and high stress correlates with higher asthma rates. 
Consider a recent case report published in The Lancet of an 18-year-old asthmatic who had recently broken up with his girlfriend. His girlfriend had “un-friended” him on Facebook, changed her profile picture, and had recently “friended” some other young men. Afterwards he would reliably become dyspneic after accessing her Facebook page, and his peak flow, as measured by his mother, would drop by up to 20% after Facebook exposure. Investigators also suggested that hyperventilation may have played a small role. 
Another point of interest is the way in which cultural and educational differences may affect patients’ interpretations of their asthma triggers. In a German study that sought to establish a German equivalent of the Asthma Triger Inventory, those who were male, married or cohabitating, and with higher levels of education all perceived fewer triggers in general. Those they did identify were more likely to be allergic rather than non-allergic triggers. Authors questioned if these disparities were purely psychosocial or were at least in part due to variation among living situations. 
Asthma negatively affects quality of life
One thing that is clear is that asthma negatively impacts our patients’ quality of life. A study utilizing the Pediatric Assessment Quality of Life Questionnaire (PAQLQ) found that greater asthma severity, as determined by steroid burst, ED visit, hospital admission, greater trigger number, and higher frequency of exacerbations correlated with a clinically significant decrease in quality of life.  Emergency Physicians are specialists in the treatment of acute exacerbations of all types of chronic diseases, but may lack the ability to fully address chronic problems during short patient interactions in the ED. However, Emergency Physicians may be able to reduce suffering, morbidity and mortality in our asthma patients by briefly reviewing triggers with them, both common and sneaky, and briefly instruct them as to how to reduce the threat of these triggers.  It is also very important to educate them in the proper use of their medications and the need for follow-up. 
Case 1 Resolution: A wide differential was considered including asthma, bronchitis, pneumonia, pneumothorax, ACS, and pulmonary embolism. The patient was treated with albuterol and ipratropium nebulizers and oral Prednisone. She was reevaluated and wheezing had resolved. Her peak flow improved to 500 L/min, and she was ambulating around the ED without difficulty or shortness of breath. Her Wells score was 0, and she met PERC rule out criteria. The patient was then questioned about possible trigger factors for her asthma. She said that she had been having a hacking cough productive of scant amounts of yellow sputum for over a week and a mild sore throat. She also said that she had been spending a lot of time lately at the house of a friend, who had a cat, and she had noticed that her asthma was worse when she was there. She was given azithromycin for a respiratory infection with a possible atypical organism, such as Mycoplasma. She was also educated about avoiding exposure to cat hair. She was subsequently discharged home on a rescue pump (albuterol), a controller pump (Flovent), a seven-day course of prednisone and the azithromycin. She was educated about the proper use of her medication, and given an urgent appointment for the Asthma Clinic. It is very important that the patient with asthma be aware of possible triggers, and educated as to how to prevent and treat their asthma exacerbations. The triggers may be multiple. 
Case 2 Resolution: The patient was treated with IM ketamine and placed on noninvasive ventilation with prolonged expiratory time (an intervention with inconclusive evidence of benefit). She subsequently received continuous in-line albuterol and ipratropium nebulizers, methylprednisolone IV, and magnesium sulfate IV. Her respiratory status improved, and intubation was avoided. Bedside ultrasound showed lung sliding in all fields without B-lines or basilar pleural effusions. CXR was negative for consolidation or pulmonary edema. EKG and cardiac biomarkers were negative for STEMI. She was admitted to telemetry on NIV, was successfully weaned to q4 hourly metered dose inhalers, and eventually discharged home. The patient was counseled about her smoking, and she was referred to a smoking cessation program. She was also counseled about the importance of losing weight, as obesity is a problem associated with exacerbation of asthma.  She was discharged on appropriate asthma medications, for which she received appropriate education, and given close clinic follow-up. Proper education regarding asthma exacerbation and the need for prompt treatment of exacerbations decreases the severity and incidence of asthma exacerbations. 
-Consider both common and “sneaky” triggers in your asthma patients.
-Common triggers include: allergic, activity-related exacerbations, air pollution, and infectious causes.
-Sneaky triggers to remember: reflux, medications (NSAIDs, ARBs), and psychological triggers.
-Assuming all patients triaged with chief complaint “asthma” actually have an asthma exacerbation. Instead, approach your asthma patient as having “shortness of breath”, and consider the wide differential diagnosis of dyspnea (asthma, pneumonia, pulmonary embolism, congestive heart failure, acute coronary syndrome, pneumothorax, etc.). Remember all that wheezes is not asthma.
-Not considering underlying dangerous causes of asthma exacerbation, such as pneumonia or anaphylaxis, and not treating the underlying cause appropriately.
Take Home Points
First: “An ounce of prevention is worth a pound of cure” as Benjamin Franklin once stated. It is important to consider the possible underlying causes of asthma exacerbations, and correct them in order to prevent them in the future.
Second: Educate your patients about triggers, both common and sneaky. Encourage handwashing, yearly flu vaccine, weight loss, proper use of medications, and additional long-term evaluation and follow up with pulmonologists.  We may be able to reduce suffering, morbidity and mortality in our asthma patients by briefly reviewing triggers with them, both common and sneaky, and strongly encouraging them to get rid of these triggers as much as possible. 
Third: If you don’t have the evidence to support that an episode of shortness of breath is an asthma exacerbation, then widen your differential and consider other causes.
References and Further Reading
- Tintinalli J, Stapczynski J, Ma O, Yealy D, Meckler G, Cline D. Tintinalli’s Emergency Medicine. 8th ed.; Chapter 69: Acute Asthma.
- Karvala K, Uitti J, Taponen S, Luukkonen R, Lehtimäki L. Asthma trigger perceptions are associated with work disability. Respir Med. 2018; 139:19-26
- McCarty J, Ferguson B. Identifying Asthma Triggers. Otolaryngol Clin North Am. 2014;47(1):109-118
- Shaker A, Mustafa A, Malik W, Iqbal T, Hassan A, Gillani A. Risk Factors of Asthma and Their Role in Triggering The Asthmatic Attack. Value in Health. 2017; 20(9):A641
- Ritz T, Kullowatz A, Kanniess F, Dahme B, Magnussen H. Perceived triggers of asthma: Evaluation of a German version of the Asthma Trigger Inventory. Respir Med. 2008;102(3):390-398
- Altman M, Babineau D, Whalen E et al. Coordinated Epithelial and Eosinophil Inflammatory Pathways Underpin Upper Respiratory Tract Viral Infection (URI) Triggered Asthma Exacerbations. Journal of Allergy and Clinical Immunology. 2018;141(2):AB110
- Ojanguren I, Genover T, Muñoz X, Ramon M, Martínez Moragon E, Morell F. Incidence and Triggers of Asthma Exacerbations Attended in the Emergency Department as a Level of Care Indicator (ASMAB III, 2005 and ASMAB IV, 2011). Archivos de Bronconeumología (English Edition). 2016; 52(2):82-87
- Webley W, Aldridge K. Infectious asthma triggers: time to revise the hygiene hypothesis? Trends Microbiol. 2015; 23(7):389-391
- Johnston SL. Azithromycin for Acute Exacerbations of Asthma: The AZALEA Randomized Clinical Trial. JAMA Internal Medicine. 176:1630-1637. doi:10.1001/jamainternmed.2016.5664
- Morales DR, Jackson C, Lipworth BJ, Donnan PT, Guthrie B. Adverse Respiratory Effect of Acute β-Blocker Exposure in Asthma. Chest. 2014;145(4):779-786. doi:10.1378/chest.13-1235
- D’Amato G, Liccardi G, Cecchi L, Pellegrino F, D’Amato M. Facebook: a new trigger for asthma?. The Lancet. 2010; 376(9754):1740
- Chipps B, Haselkorn T, Rosén K, Mink D, Trzaskoma B, Luskin A. Asthma Exacerbations and Triggers in Children in TENOR: Impact on Quality of Life. The Journal of Allergy and Clinical Immunology: In Practice. 2018; 6(1):169-176.e2
- Gruber K, McKee-Huger B, Richard A, Byerly B, Raczkowski J, Wall T. Removing asthma triggers and improving children’s health. Annals of Allergy, Asthma & Immunology. 2016; 116(5):408-414