Symptom patterns emerge in NSAID-exacerbated respiratory disease development
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Key takeaways:
- Patients who experienced asthma first were younger.
- Patients with NSAID sensitivity first were mostly male.
- Polyp onset was at a mean age of 35 years among patients with polyps first.
Age, sex, ethnicity, BMI and environmental exposures were associated with different patterns in NSAID-exacerbated respiratory disease development, according to a study in The Journal of Allergy and Clinical Immunology: In Practice.
These patterns may help clinicians better detect disease and guide treatment, Kelley Nicole Dages, MD, a fellow in the division of allergic diseases of the department of medicine at Mayo Clinic in Rochester, Minnesota, and colleagues wrote.
The researchers prospectively interviewed 240 adults (68% women; 77% non-white) with NSAID hypersensitivity, nasal polyposis and asthma, which are considered the symptom triad of NSAID-exacerbated respiratory disease (NERD).
Presentation groups
The sequence of NERD development began with asthma for 50% of the patients, rhinitis/nasal polyps for 29%, NSAID hypersensitivity for 16% and all symptoms concurrently for 5%.
The researchers confirmed NSAID hypersensitivity with an in-office graded challenge to aspirin for 224 patients (93.3%). Diagnoses for the other 16 patients came from their histories.
The 64 patients (27%) who were not aware of their NSAID allergy at the time of their initial presentation had a median delay in diagnosis of 3 years (interquartile range [IQR], 0-5 years). Also, 48 of these patients did not take NSAIDs routinely, so their hypersensitivity was the last symptom in the triad diagnosed, with a median delay of 3 years (IQR, 0-5 years) from their development of asthma or polyps.
The 186 patients with a history of environmental allergies included 108 (58%) with documented sensitization to indoor allergens and 113 (61%) with documented sensitization to outdoor allergens. Additionally, 129 of the 220 patients (59%) with a history of environmental pollutant exposure reported excessive exposure.
The patients who reported asthma as the earliest symptom in the triad were 72% women and, at a mean age of 25 years at initial symptom onset, were significantly younger than other presentations (P < .001). Once these patients developed asthma, they developed nasal polyps at a mean age of onset of 35 years and NSAID sensitivity at a mean age of 37 years.
The patients who reported rhinitis/sinusitis or nasal polyps first were 70% women with onset at a mean age of 35 years, with asthma developing at a mean age of onset of 38 years and NSAID sensitivity at age 42 years.
The patients who reported NSAID sensitivity before other symptoms were 51% men with onset at a mean age of 35 years. These patients were more likely to report exposure to environmental pollution (81%; P = .002) and had higher baseline IgE levels (290 IU/mL; IQR, 146-525; P = .009) than the other groups. Once these patients developed NSAID hypersensitivity, onsets included a mean age of 39 years for asthma and age 40 years for nasal polyps.
The patients who developed all three symptoms in the triad simultaneously were 83% women with an onset at mean age 33 years, with lower baseline IgE levels (98 IU/mL; IQR, 43-154) than the other groups (P = .009).
Link between exposures, presentation
The researchers called the differences in percentages of patients with histories of excessive exposure to pollution (P = .002) and infestation (P = .02) between the groups significant. By race and ethnicity, 76% of Latino patients, 63% of Black patients, 52% of patients of other race and 44% of white patients reported pollution exposure (P = .006).
Although 78% of patients overall had a history of indoor and/or outdoor allergies, the researchers found no significant associations between the sequence of symptoms in the triad and the presence of these allergies.
Compared with the other sequences, the asthma-first sequence had a significant association with BMI, including an odds ratio of 1.3 (95% CI, 1.06-1.7) per five BMI units.
Also, younger ages of asthma onset were associated with female sex (OR = 5.3; 95% CI, 1.4-20), Latino ethnicity (OR = 6.7; 95% CI, 1.3-34) and higher BMI (OR per five BMI units = 1.5; 95% CI, 1.01-2.3).
The polyps-first sequence was associated with older age of NSAID hypersensitivity onset (OR = 1.03; 95% CI, 1.01-1.06).
The NSAID hypersensitivity-first sequence had a significant association with male sex (OR = 3.3; 95% CI, 1.5-7.4) and pollution exposure (OR = 4.4; 95% CI, 1.6-11.9).
Although NERD typically starts in the third or fourth decades of life, with more of an impact on women, the researchers said, symptom onsets vary and the disease could follow complex modeling pathways from development to diagnosis.
An understanding of these potential risk factors and progression is key to the physician’s ability to recognize and treat the disease in a timely manner, the researchers continued, and the ability to predict the course of the disease based on these factors is now a tangible goal.
Perspective
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This study provides real-world data that may help providers better characterize NERD. In particular, it is significant that not all patients follow the same pattern in symptom onset.
Although many providers learn the “classic” progression of the Samter’s Triad with asthma first, followed by nasal polyposis and finally NSAID sensitivity, these authors found that more than one-quarter of patients developed nasal polyps first and 16% presented with NSAID sensitivity as the first symptom, which is an important reminder that patients do not always fit the textbook.
Similar to the authors, I have found that some patients may be unaware of their diagnosis, particularly if they do not frequently take NSAIDs. In this study, the median delay in diagnosis was 3 years. This is a reminder of the importance of inquiring about specific symptoms with all patients with asthma, particularly those with nasal polyps as well.This is an important initial work that suggests significant variability in how NERD presents clinically from disease progression and demographic perspectives. However, it is a single-center study. Future studies should continue to explore these associations in other populations to see if there are predictable patterns that can help guide diagnosis and management plans for individual patients.
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