Aspirin-induced asthma is a specific syndrome affecting asthmatic patients, consisting of chronic rhinosinusitis, nasal polyps, and asthma attacks caused by aspirin and other non-steroidal anti-inflammatory cyclooxygenase enzyme inhibiting drugs. The asthma episode is accompanied by acute rhinosinusitis. Symptoms occur 30 minutes to 3 hours after the drug is ingested.
Presentation
Women are twice more likely to be affected by aspirin-induced asthma. Symptoms usually develop gradually over several years [1], but patients with rapid progression have also been described [2]. If patients are atopic, chronic rhinitis and asthma occur earlier in life, unlike aspirin intolerance and nasal polyps [3]. The sense of smell is diminished in these patients [4]. Chronic asthma may have any severity. Even mild, intermittent asthma patients may have acute episodes induced by aspirin consumption and up to one-quarter of patients that need to be admitted to the hospital due to a crisis have ingested non-steroidal anti-inflammatories during the last 3 hours [5]. Respiratory symptoms (wheezing, dyspnea, cough) and chest pain [6] that that radiates to the jaw or arms and is accompanied by diaphoresis and nausea develop together with nasal obstruction or rhinorrhea, periorbital edema, facial flushing or macular rash [7] and conjunctival injection. Less frequently, patients also have abdominal pain, hypotension, and laryngospasm.
If nasal polyps are removed, they tend to recur. Sinus mucosa is also polypoidal and hypertrophied. The initial episode of rhinitis in these patients often occurs after a viral infection [8].
Respiratoric
- Dyspnea
The bronchial response (BR) was evidenced by dyspnea and spirometry, whereas the nasal response (NR) was evidenced by nasal symptoms and acoustic rhinometry and/or rhinomanometry. [ncbi.nlm.nih.gov]
It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea ( DYSPNEA, PAROXYSMAL ). [hon.ch]
Respiratory symptoms (wheezing, dyspnea, cough) and chest pain that that radiates to the jaw or arms and is accompanied by diaphoresis and nausea develop together with nasal obstruction or rhinorrhea, periorbital edema, facial flushing or macular rash [symptoma.com]
[…] characteristic symptoms of asthma (e.g., wheezes, congestion, dyspnea ) are absent. [amboss.com]
Chiu 18 18 Congenital MVP,ASA.No regurgitation. dyspnea, dizziness worse with TDF/FTC/RAL Dr blames Dr. John Chiu Dr. Chiu Confusing: You need to use less abbreviations and provide a clearer description. [healthtap.com]
- Bronchospasm and Wheezing
Albuterol administered by a nebulizer or through an inhaler (with good inhaler technique) can help with bronchospasm ( cough, wheezing, chest tightness ). It is imperative to avoid all Aspirin products and nsaids like ibuprofen. [healthtap.com]
Workup
The diagnosis of aspirin induced asthma is made from the history and clinical examination. In uncertain cases, challenge tests may be useful [8] for confirmation of the diagnosis. But, as they can provoke severe asthmatic episodes, they should only be performed in the hospital and aspirin can be administered by various routes: oral, nasal, bronchial and intravenous, in increasing doses for four consecutive days. Following administration, if a fall in forced expiratory volume in one second of at least 20% is observed, the test is considered positive [9]. Patients should receive leukotriene-modifying agents before the test because they have been proven to diminish the severity of bronchial constriction, while nasal and ocular symptoms tend to still appear, so the clinician can interpret the results of the test as positive. If lysine- aspirin is administered by inhalation route, only bronchial symptoms will occur. Inhalation tests may remain negative even in patients with positive oral tests. Oral and bronchial tests have similar specificity, but the oral test is more sensitive.
Several tests have been used over the years: histamine, methacholine, allergens and lysine-aspirin [10]. The Aspirin Sensitive Patient Identification Test is a new method to prove aspirin intolerance that still needs further validation [11].
Additional diagnostic methods include computer tomography scans of paranasal sinuses, that show mucosal hypertrophy and polyps. If the sinuses appear normal, the likelihood of aspirin-induced asthma is low.
Most patients are atopic [12] and some have increased respiratory antigen immunoglobulin E levels [13]. The peripheral eosinophil count can be high [14] and eosinophils are frequently found in the nasal and bronchial mucosa. The skin prick tests may be also positive for aeroallergens [15].
Serum
- Antinuclear Autoantibodies
Antinuclear autoantibodies of SS-B specificity were present in the serum. Challenge with aspirin provoked asthma and distinct blood circulation disturbance in the hands. [ncbi.nlm.nih.gov]
Treatment
Weekly mean values of symptom scores were generally lower and PNIF measurements higher during treatment with FP than with placebo. This difference was statistically significant for most recorded parameters for the whole 4-week FP treatment. [ncbi.nlm.nih.gov]
At 4 h after the first dose of treatment the increase in FEV1 was seen only on zileuton treatment days; the treatment difference was 7.5% (95% CI, 3–12%; p < 0.01) corresponding to 0.18 L. [atsjournals.org]
Aspirin desensitization in the treatment of chronic rhinosinusitis. Curr Allergy Asthma Reports 2006, 6: 183–184. CrossRef Google Scholar 38. [doi.org]
Prognosis
Treatment and prognosis Treatment is largely centered around avoiding aspirin, treating underlying asthma and if need be polypectomy (surgical or medical). Unfortunately recurrences are common 2. [radiopaedia.org]
Etiology
Abstract The etiology of aspirin-sensitive asthma is unknown, but a plausible hypothesis is that the inhibitory effect of aspirin on the cyclooxygenase enzyme increases formation of bronchoconstrictor leukotrienes via "shunting" of unmetabolized arachidonic [ncbi.nlm.nih.gov]
The etiology of ASA induced asthma is complex and not fully understood, but most evidence points towards an abnormality of arachidonic acid (AA) metabolism. [eurekaselect.com]
Asthma is a phenotypically heterogeneous disorder with many etiologic factors and clinical characteristics. T-bet, a Th1-specific transcription factor of T-box family, has been found to control interferon-gamma (IFN-gamma) expression in T cells. [uniprot.org]
Epidemiology
Kevin Li, Andrew Lee and Waleed Abuzeid, Aspirin Exacerbated Respiratory Disease: Epidemiology, Pathophysiology, and Management, Medical Sciences, 10.3390/medsci7030045, 7, 3, (45), (2019). [doi.org]
Acetaminophen and the risk of asthma: The epidemiologic and pathophysiologic evidence. Chest. 2005;127(2):604-12. [Abstract | Full text] Hedman J, Kaprio J, Poussa T, Nieminen MM. [myvmc.com]
Pathophysiology
James Bartley, Nutrition and the Upper Respiratory Tract, Nasal Physiology and Pathophysiology of Nasal Disorders, 10.1007/978-3-642-37250-6_14, (183-190), (2013). [doi.org]
These two nonspecific triggers may also share pathophysiologic mechanisms, including mast cell and leukotriene-related pathways, and may be related to vascular response–mediated airway narrowing. [accessmedicine.mhmedical.com]
She was awarded PhD and DSc degrees in specialities of pulmonology and pathophysiology in 1992 and 2002. She is a member of the European Respiratory Society (ERS) and European Network on Aspirin-Induced Asthma (AIANE). [books.google.com]
Redegeld Affiliation: Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. [eurekaselect.com]
Prevention
Avoiding ASA and nonsteroidal anti-inflammatory drugs does not prevent progression of the inflammatory disease. Corticosteroids continue to be the mainstay of therapy, and anti-LT drugs are also indicated for treatment of the underlying disease. [ncbi.nlm.nih.gov]
Mast-cell stabilizers are used prophylactically to prevent asthma attacks and the manifestations of seasonal or chronic allergic rhinitis. Cromolyn and Nedocromil are the common mast cell stabilizing drugs. [healthunits.com]
References
- Fahrenholz JM. Natural history and clinical features of aspirin-exacerbated respiratory disease. Clin Rev Allergy Immunol. 2003; 24:113.
- Szczeklik A, Nizankowska E, Duplaga M. Natural history of aspirin-induced asthma. AIANE Investigators. European Network on Aspirin-Induced Asthma. Eur Respir J. 2000; 16:432.
- Sturtevant J. NSAID-induced bronchospasm: a common and serious problem; a report from MEDSAFE, the New Zealand medicines and medical devices safety authority. NZ Dent J. 1999; 95:84
- Ta V, White AA. Survey-Defined Patient Experiences With Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract. 2015; 3:711.
- Marquette CH, Saulnier F, Leroy O, et al. Long-term prognosis of near-fatal asthma: a 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis. 1992; 146:76-81.
- Shah NH, Schneider TR, DeFaria Yeh D, et al. Eosinophilia-Associated Coronary Artery Vasospasm in Patients with Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract. 2016; 4:1215.
- Cahill KN, Bensko JC, Boyce JA, Laidlaw TM. Prostaglandin D₂: a dominant mediator of aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2015; 135:245.
- Szczeklik A, Stevenson DD. Aspirin-induced asthma: advances in pathogenesis and management. J Allergy Clin Immunol 1999;104:5–13.
- Dahlen B, Zetterström O. Comparison of bronchial and peroral provocation with aspirin in aspirin-sensitive asthmatics. Eur Respir J. 1990; 3:527–534,
- Pawlowicz A, Williams W, Davies B. Inhalation and nasal challenge in the diagnosis of aspirin-induced asthma. Allergy. 1991; 46:405–409
- Jedrzejczak-Czechowicz M, Lewandowska-Polak A, Bienkiewicz B, Kowalski ML. Involvement of 15-lipoxygenase and prostaglandin EP receptors in aspirin-triggered 15-hydroxyeicosatetraenoic acid generation in aspirin-sensitive asthmatics. Clin Exp Allergy. 2008;38(7):1108-16
- Dursun AB, Woessner KA, Simon RA, et al. Predicting outcomes of oral aspirin challenges in patients with asthma, nasal polyps, and chronic sinusitis. Ann Allergy Asthma Immunol. 2008;100:420.
- Barranco P, Bobolea I, Larco JI, et al. Diagnosis of aspirin-induced asthma combining the bronchial and the oral challenge tests: a pilot study. J Investig Allergol Clin Immunol 2009;19:446.
- Fountain CR, Mudd PA, Ramakrishnan VR, et al. Characterization and treatment of patients with chronic rhinosinusitis and nasal polyps. Ann Allergy Asthma Immunol. 2013; 111:337.
- Kalyoncu AF, Karakaya G, Sahin AA, et al. Occurrence of allergic conditions in asthmatics with analgesic intolerance. Allergy. 1999;54:428–435.