As winter loosens its grip across Western Pennsylvania and dormant trees begin to bud, pollen returns with a vengeance, ushering in yet another allergy season. Patients across the region are all too familiar with the symptoms: runny noses, itchy eyes, and persistent congestion. For many, these are just an inconvenience, but for others, allergies can significantly affect daily life or even trigger serious respiratory conditions like asthma. Faculty in the Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine (PACCSM) are addressing both challenges, improving symptom management while investigating why some forms of asthma fail to respond to standard therapies.
During peak allergy months, allergists, like Andrej Petrov, MD, see a surge in patients reporting nasal congestion, sneezing, postnasal drainage, sinus pressure, and watery eyes. Many also experience fatigue, poor sleep, and reduced productivity. For those with asthma, allergy season can intensify wheezing, coughing, and shortness of breath. Petrov notes that in Western Pennsylvania, the geography and climate amplify these effects significantly, with hills and river valleys impacting wind patterns, resulting in higher concentrations of pollen in the air.
Complicating things further, patients often mistake seasonal allergies with viruses, such as colds or COVID. Allergist Merritt Fajt, MD, notes that while allergies can share symptoms with these illnesses, there are key differences to help distinguish them. “Seasonal allergy symptoms can last for weeks to months and often worsen when patients are outdoors or on days when pollen counts are high. Patients with seasonal allergies often experience ocular itching and redness as well as repetitive sneezing attacks and nasal itching which are rare in patients with viral infections such as the common cold or COVID.” Viral infections, by contrast, are more likely to include fever, body aches, or loss of taste and smell. Recognizing these differences is critical, particularly for patients with asthma, who may experience both upper and lower airway symptoms.
Despite these differences, many patients with seasonal allergies report that their symptoms are severe and feel like they have a “never-ending cold.” Consequently, their quality of life is severely impacted and leads to impaired sleep, social activities, and work productivity. In some cases, this leads to patients that are frequently treated unnecessarily for sinus infections with multiple antibiotic courses and often receive systemic corticosteroid treatments, which can have serious side effects.
And, for some patients, allergies can do more than irritate the nose and eyes; they can also trigger or worsen asthma. Environmental strategies, like staying indoors during high-pollen days or using air filtration, can help, but they are often impractical, especially for patients sensitive to multiple allergens. Moreover, allergies themselves are becoming more common due to changes in vegetation, urbanization, and climate. In fact, over the past three decades, North American allergy seasons have lengthened by roughly 20 days, with pollen levels rising significantly – a trend expected to continue.
Many over-the-counter treatments, such as antihistamines, nasal sprays, and eye drops, help control symptoms, but they may not address asthma-related inflammation. When symptoms persist, evaluation by an allergy or immunology specialist can help confirm diagnoses and guide treatment, from over-the-counter options to allergy shots and prescription medication. Additional therapies are also expanding treatment options, including sublingual immunotherapy for those with a single allergen, and targeted biologic therapies may eventually provide new options for patients with severe allergic disease.
While these approaches may manage immediate symptoms, seasonal surges also underscore deeper questions as to why some individuals develop more severe disease, and why others fail to respond to standard treatments. Now understood as a complex inflammatory condition, asthma can vary widely between patients. While corticosteroids remain a cornerstone of treatment, up to 30% of patients experience steroid-refractory severe asthma, which does not respond adequately to standard therapies.
Researchers like Anuradha Ray, PhD, are investigating why that is, by examining the underlying causes of this resistance, including differences in immune responses and airway biology. In some patients, inflammation is driven by pathways that do not respond to corticosteroids, while in others, molecular signaling may limit treatment effectiveness altogether. Ray and Sally Wenzel, MD, co-lead an NIH program project grant, “Immune Airway–Epithelial Interactions in Steroid-Refractory Severe Asthma,” which is looking at how the airway epithelium – the body’s first line of defense against environmental exposures – can become compromised, allowing pollutants, allergens, and viruses to trigger ongoing inflammation. Strengthening this barrier may offer a new path for treatment.
“With the emergence of single cell RNA sequencing technology, allowing us the ability to study individual cells, it is increasingly likely that several different subtypes of cells exist, as epithelial cells themselves (in healthy people) are not all the same. It appears that the epithelial cells in asthma patients are more metabolically stressed out, which leads to both effects on their ability of the cells to differentiate normally into mature cells and which likely drives more interactions with immune cells, through various inflammatory pathways.”
Building on this work, junior faculty in the division, including Marc Gauthier, MD, and Richard Ramonell, MD, are improving biomarkers for better patient stratification, allowing for more targeted and effective therapies. Current biomarkers for asthma, such as absolute blood eosinophil numbers, fraction exhaled nitric oxide (FeNO), and serum IgE levels, do not adequately reflect the heterogeneity in the underlying immune and epithelial dysfunction driving disease. Research in the Ray and Wenzel labs have shown patients may present with very similar biomarkers at initial evaluation and yet may have district ongoing immune and epithelial dysfunction in their airways.
“In our published study, the biomarkers failed to distinguish between the two groups of patients with severe asthma since Type 2 (T2) cytokines (classically associated with asthma pathogenesis) was common to both, although the second group also harbored a heightened Type 1 (T1) response. The T1 response is poorly responsive to CSs or to the currently available T2-directed biologics and thus disease alleviation in these patients requires a different approach. The mixed T1/T2 phenotype in some severe asthma patients that we initially described has been replicated in studies of other asthma cohorts. These patients are among the sickest, but they are not readily distinguishable using the available biomarkers.”
Additional advances in asthma research have revealed a highly diverse landscape of asthma pathophysiology. This diversity largely reflects aberrant activation of one or more pathways in both immune and non-immune cells, which can vary substantially among individuals with asthma being influenced by gene-environment interactions. As a result, responses to environmental triggers depend on which biological pathways are active in each individual and how effectively these pathways are controlled by ongoing treatment.
As allergy seasons grow longer and asthma remains highly variable, PACCSM clinicians and researchers at Pitt are continuing to work towards a more personalized approach that accounts for each patient’s unique biology, environment, and lifestyle, with the goal of improving control and quality of life.