Njira Lugogo, MD, from University of Michigan.

Njira Lugogo, MD

Tezepelumab Reduces Severe Asthma Exacerbations by 70% in Phase 4 PASSAGE

Real-world phase 4 PASSAGE data presented at the 2

026 American Thoracic Society (ATS) International Conference 

in Orlando, Florida, found that tezepelumab (Tezspire) reduced severe asthma exacerbations by 70%. The treatment also improved disease control across a diverse population of patients with severe uncontrolled 

, including groups routinely excluded from or underrepresented in pivotal trials.

 at ATS 2026, Njira Lucia Lugogo, MD, clinical professor of medicine in the Division of Pulmonary and Critical Care Medicine at the University of Michigan, discussed the implications of the data for real-world prescribing and the need for more inclusive trial design going forward.

PASSAGE Study Design: Real-World Severe Asthma Cohort

PASSAGE was a phase 4, multicenter, single-arm, open-label study enrolling patients aged ≥ 12 years with severe asthma and ≥ 2 exacerbations in the prior year. The 286-patient cohort was intentionally designed to reflect populations underrepresented in randomized controlled trials: 42% had blood eosinophil counts (BEC) ≥ 300 cells/µL, 58% had a positive allergy status, 22% were Black or African American, 7% were adolescents, 20% had comorbid COPD, and 29% were current or former smokers.

Tezepelumab Reduced Annualized Asthma Exacerbation Rate by 70% Overall

The annualized asthma exacerbation rate (AAER) decreased by 70% (95% CI: 63 to 75) from baseline to the treatment period overall. Across asthma phenotypes and underrepresented subgroups, reductions ranged from 54% to 77%, indicating consistent benefit regardless of eosinophil status, smoking history, or comorbid COPD.

"When we scaled up from the very homogeneous clinical trial population to a real-world population, we are replicating the effects and maybe even seeing more profound exacerbation reduction, which is very reassuring," Lugogo told 

. "It should give us the confidence that we can use these drugs in clinical practice successfully."

Tezepelumab Improved FEV1, with Greater Gains in Patients with Impaired Lung Function

At week 52, the least-squares mean change in pre-bronchodilator FEV1 from baseline was 0.12 L (95% CI: 0.07 to 0.17) overall (n = 222). Among patients with baseline FEV1 ≤ 80% predicted — those with the most compromised lung function at enrollment — the improvement was greater, at 0.21 L (95% CI, 0.15 to 0.28; n = 138).

Clinically Meaningful Improvements in Asthma Control and Quality of Life

Clinically meaningful improvements from baseline, defined by minimum clinically important difference thresholds, were observed at week 52 across three validated instruments. Among the overall population (all n = 219), 74% achieved meaningful improvement on the Asthma Control Questionnaire-6 (ACQ-6), 63% on the Asthma Impairment and Risk Questionnaire (AIRQ), and 80% on the St. George's Respiratory Questionnaire (SGRQ). Across asthma phenotypes and underrepresented populations, response rates ranged from 64 to 86% for ACQ-6, 51 to 75% for AIRQ, and 63 to 91% for SGRQ.

Tezepelumab Efficacy in Black/African American Patients with Severe Asthma

Black and African American patients comprised 22% of the PASSAGE cohort, which is a proportion greater than what is typically seen in phase 3 severe asthma trials. Lugogo noted that this population responded well to tezepelumab without new safety signals and framed the findings in the context of a broader access gap.

"Many biologic-eligible patients are simply not receiving any biologic, so I'm hoping that this new data…is going to give us more confidence, and we'll be able to increasingly use biologics in wider patient populations,” Lugogo said.

Tezepelumab Safety Profile Consistent With Prior Trial Data

In total, 28 patients (9.8%) experienced a serious adverse event during the treatment period following tezepelumab initiation. Adverse events were consistent with the established safety profile of the drug.

PASSAGE Highlights Gaps in Severe Asthma Trial Design

Beyond the clinical findings, Lugogo called for a broader reconsideration of how severe asthma trials are structured. Patients with comorbid asthma-COPD overlap remain ineligible for most interventional trials, leaving clinicians without prospective evidence until post-authorization studies like PASSAGE are completed.

"We need to think about whether we need a paradigm shift in how we design our trials to include some of these comorbid populations so that we can have data a bit earlier and not have to wait for data generation afterwards,” Lugogo said.

Watch part 1 of our interview with Lugogo here: 

Tezepelumab Reduced Severe Asthma Across Phenotypes in Phase 4 PASSAGE.

Editor’s note: Relevant disclosures for Lugogo include GlaxoSmithKline, GENZYME CORPORATION, SANOFI-AVENTIS U.S., AstraZeneca Pharmaceuticals, Regeneron Pharmaceuticals, Incyte Corporation, and more.

Lugogo NL, Akuthota P, Sumino K, et al. (

) Tezepelumab in diverse real-world patients with severe asthma across different phenotypes and underrepresented populations: final results from the US phase 4 PASSAGE study. Late-breaking research was presented at the American Thoracic Society 2026 International Conference on May 18 in Orlando, Florida.

Videos

Phase 4 PASSAGE data from ATS 2026 show tezepelumab reduced exacerbation rates across a diverse real-world cohort, including smokers, adolescents, and patients with comorbid COPD.

HCPLive Five at Asthma Updates at ATS 2026

HCPLive Five: Asthma Updates at ATS 2026

2026 American Thoracic Society (ATS) International Conference

 in Orlando, Florida, with new data challenging long-held assumptions about who benefits from biologic therapy and how to measure that benefit.

 — Tezepelumab: 70% exacerbation reduction across phenotypes including smokers and comorbid COPD (PASSAGE).

 — Dupilumab: nearly 2x remission odds; 4x wins in "hot-hot" eosinophil/FeNO patients (QUEST win ratio analysis).

 — Tezepelumab: 2.93x greater OCS reduction vs placebo; 36% discontinued OCS entirely (SUNRISE).

 — Periconception eosinophils: each 100 cells/µL increase linked to 0.20 additional exacerbations (P <.001).

 — Depression: 2x odds of poorly controlled asthma independent of BMI, race, and socioeconomic status.

Expert interviews from ATS 2026, Orlando.

In this HCPLive Five, 5 physician experts share findings that expand the treatment conversation beyond traditional phenotypes: tezepelumab demonstrating efficacy in active smokers and patients with comorbid chronic obstructive pulmonary disease (COPD), dupilumab pushing toward remission in high-inflammation type 2 disease, and a first look at periconception eosinophils as a pregnancy risk biomarker. Rounding out the lineup, new oral corticosteroid (OCS) reduction data from phase 3 SUNRISE and an analysis on depression and asthma control underscore how much of the disease burden still goes unaddressed in routine clinical practice.

Depression Doubles Poorly Controlled Asthma Odds but Goes Unscreened

Depression and Poor Asthma Control Call for Mental Health Attention, With Brittany Duchene, MD

Depressive symptoms were associated with twice the odds of poorly controlled asthma yet showed no significant differences in exacerbation rates or spirometry, according to research presented at ATS 2026 by Brittany Duchene, MD, of the University of Vermont Medical Center. The cross-sectional analysis pooled data from three American Lung Association cohorts (n = 741) using PHQ-9 and CES-D screening tools. BMI emerged as an independent predictor of urgent healthcare utilization, with data suggesting even 5% body weight reduction improves asthma outcomes. Duchene called the depression-asthma control discordance an important and underrecognized gap warranting routine mental health screening in asthma management.

Tezepelumab Reduces Severe Asthma Exacerbations in Smokers and Comorbid COPD Patients: PASSAGE

Tezepelumab Reduced Severe Asthma Across Phenotypes in Phase 4 PASSAGE, With Njira Lugogo, MD

Tezepelumab reduced annualized asthma exacerbation rates by 70% over 52 weeks in the phase 4 PASSAGE study, with consistent reductions of 54 to 77% across phenotypes, including active smokers, patients with comorbid COPD, and those with low eosinophil counts, according to data presented at ATS 2026. Njira Lugogo, MD, director of the asthma program at the University of Michigan, highlighted that these traditionally underrepresented populations showed treatment effects comparable to the broader cohort. Patient-reported outcomes improved significantly across ACQ-6, AIRQ, and SGRQ measures. Lugogo noted the findings challenge the common clinical practice of withholding biologics from patients who have not yet stopped smoking.

Dupilumab Nearly Doubles Remission Odds in Type 2 Asthma With Elevated Eosinophils and FeNO

Dupilumab Nearly Doubled Remission Odds in Type 2 Asthma, With Simon Couillard, MD

Dupilumab nearly doubled the odds of achieving clinical remission in moderate-to-severe type 2 asthma, with patients showing both elevated eosinophils (≥ 300 cells/μL) and high FeNO (≥ 35 ppb) demonstrating 4-fold greater remission wins, according to a win ratio analysis of the phase 3 QUEST trial presented at ATS 2026. Simon Couillard, MD, of the Université de Sherbrooke, applied a hierarchical endpoint framework prioritizing exacerbation elimination, lung function, and symptom control. Couillard advocated for routine eosinophil and FeNO biomarker screening to identify optimal biologic candidates earlier and called remission an achievable, though currently treatment-dependent, target in asthma care.

Periconception Eosinophil Counts Predict Asthma Exacerbations During Pregnancy

Periconception Eosinophil Counts Predict Asthma Exacerbations in Pregnancy, With Christian Cardillo, MD

Periconception eosinophil counts were independently associated with increased asthma exacerbation frequency during pregnancy, with each 100 cells/µL increase linked to 0.20 additional exacerbations (

 <.001), according to late-breaking data presented at ATS 2026 by Christian Cardillo, MD, of Lewis Katz School of Medicine at Temple University Hospital. The single-center study of 31 pregnant patients suggests eosinophils, already part of routine CBC testing around 8–12 weeks’ gestation, could serve as a scalable biomarker for identifying high-risk type 2 inflammatory asthma phenotypes earlier in pregnancy. Cardillo called findings exploratory but noted prospective validation could support earlier pulmonology or maternal-fetal medicine referrals.

Tezepelumab Cuts Oral Corticosteroid Use by Nearly Two-Thirds in Severe OCS-Dependent Asthma: SUNRISE

Phase 3 SUNRISE: Tezepelumab Shows Meaningful OCS Reduction in Severe Asthma, With Michael E. Wechsler, MD

Phase 3 SUNRISE trial data presented at ATS 2026 showed tezepelumab-treated patients were nearly 3 times more likely to achieve meaningful oral corticosteroid (OCS) reduction versus placebo (cumulative OR 2.93; 

 =.003) in severe OCS-dependent asthma, with 36% discontinuing OCS entirely. Michael Wechsler, MD, of National Jewish Health, noted the findings align with prior SOURCE trial and real-world Wayfinder data, reinforcing tezepelumab's consistent evidence base.

Beyond OCS reduction, tezepelumab improved pre-bronchodilator FEV1 and asthma control scores. Wechsler highlighted the drug's upstream TSLP-blocking mechanism—inhibiting IL-4, IL-5, and IL-13 pathways—as key to its broad, phenotype-spanning efficacy.

Looking for more ATS 2026 coverage? Don't miss our 

HCPLive Five on late-breaking phase 3 pulmonology data 

featuring expert interviews on AD109 for OSA, ralinepag for PAH, ALIS for MAC lung disease, and more.

Editor’s note: Disclosures include GlaxoSmithKline, GENZYME CORPORATION, SANOFI-AVENTIS US, AstraZeneca Pharmaceuticals, Regeneron Pharmaceuticals, and Incyte Corporation for Lugogo; AstraZeneca Pharmaceuticals and GlaxoSmithKline for Cardillo; and SANOFI-AVENTIS US, GENZYME CORPORATION, GlaxoSmithKline, Merck Sharp & Dohme, AstraZeneca Pharmaceuticals for Wechsler. Duchene and Couillard have no reported disclosures. 

5 interviews. 5 minutes. The asthma data from ATS 2026 your patients will be asking about.

Tezepelumab Reduced Severe Asthma Across Phenotypes in Phase 4 PASSAGE

Final results from the phase 4 PASSAGE study presented at the 

American Thoracic Society (ATS) 2026 International Conference

 in Orlando, Florida, suggest tezepelumab may provide meaningful clinical benefit across a broad spectrum of patients with severe uncontrolled 

, including populations frequently excluded from biologic trials, such as active smokers and patients with comorbid chronic obstructive pulmonary disease (COPD). Pivotal trials often exclude these populations because of concerns that smoking-related airway inflammation may blunt treatment response.

The multicenter, single-arm, open-label study evaluated tezepelumab in a diverse US real-world cohort of 286 patients aged ≥ 12 years with severe asthma and ≥ 2 exacerbations in the previous year. Investigators specifically enrolled patients representing different inflammatory phenotypes and traditionally underrepresented populations, including Black/African American patients, adolescents, smokers with ≥ 10 pack-years, and patients with mild-to-moderate comorbid COPD.

According to study findings, annualized asthma exacerbation rates (AAERs) declined by 70% overall after 52 weeks of treatment with tezepelumab (95% confidence interval [CI], 63 to 75). Reductions across phenotypes and underrepresented populations ranged from 54% to 77%, with consistent improvements observed regardless of eosinophil count or allergic status.

“The PASSAGE study was really important [because it included] … populations that were not part of the phase 3 clinical program,” Njira Lugogo, MD, professor of internal medicine and director of the asthma program at the University of Michigan, said in an interview at ATS 2026. The [group]… I was most excited about [was patients] with comorbid COPD and…previous or current smokers, because we really don’t have data on those patients.”

Tezepelumab targets thymic stromal lymphopoietin (TSLP), an epithelial cytokine positioned upstream in the inflammatory cascade. Because TSLP can be activated by multiple triggers, including allergens, infections, pollutants, and environmental exposures, investigators have hypothesized the therapy may provide benefit across diverse asthma phenotypes.

PASSAGE findings appeared to support that premise. Patients with eosinophilic and allergic asthma demonstrated robust responses, but clinically meaningful improvements were also observed in patients without elevated eosinophils or perennial allergen sensitization.

Lugogo noted that this broad activity is particularly relevant in routine clinical practice, where many patients have overlapping triggers and mixed inflammatory profiles.

“The majority of patients in PASSAGE actually had multiple triggers,” Lugogo said. “As a clinician, it’s important to know I can treat a broad population of patients, and I can target some of those triggers that many of our patients are exposed to.”

In addition to reductions in exacerbations, PASSAGE demonstrated improvements across multiple patient-reported outcome measures. Clinically meaningful improvements were observed in the Asthma Control Questionnaire-6 (ACQ-6; 74%), Asthma Impairment and Risk Questionnaire (AIRQ; 63%), and St George’s Respiratory Questionnaire (SGRQ; 80%) scores in most patients at week 52. The team observed improvements in these scores across asthma phenotypes and underrepresented populations: ACQ-6 (64% to 86%), AIRQ (51% to 75%), and SGRQ (63% to 91%).

Investigators also reported gains in lung function. Mean pre-bronchodilator forced expiratory volume in 1 second (FEV1) increased by 0.12 L overall, with larger improvements (0.21 L increase) among patients with baseline FEV1 ≤ 80% predicted.

Safety findings were consistent with the known profile of tezepelumab. Serious adverse events were reported in 9.8% of patients during treatment, with no unexpected safety concerns identified.

Among patients with comorbid COPD and smokers, tezepelumab demonstrated treatment effects similar to those observed in the broader study population. Lugogo said the consistency of benefit in these groups was somewhat unexpected and could have important implications for biologic eligibility decisions in clinical practice.

“Some clinicians withhold biologics until patients stop smoking,” Lugogo said. “But it’s very difficult to stop smoking, and the steroids we are giving patients are toxic. This reassures us that we can treat these active smokers and people with a significant smoking history with biologics while working to reduce their reliance on tobacco products.”

Editor’s note: Relevant disclosures for Lugogo include GlaxoSmithKline, GENZYME CORPORATION, SANOFI-AVENTIS U.S, AstraZeneca Pharmaceuticals, Regeneron Pharmaceuticals, Incyte Corporation, and more.

) Tezepelumab in Diverse Real-World Patients With Severe Asthma Across Different Phenotypes and Underrepresented Populations: Final Results from the US Phase 4 PASSAGE Study. Late breaker was presented at ATS 2026 on May 18.

At ATS 2026, Njira Lugogo, MD, discussed PASSAGE data showing tezepelumab reduced severe asthma exacerbations in smokers and patients with comorbid COPD.


Mucus plugs are an increasingly present issue in uncontrolled asthma. Lugogo discusses promising findings from VESTIGE that addresses them.

Dupilumab Reduces Mucus Burden in Uncontrolled Asthma, with Njira Lugogo, MD

Dupilumab improved mucus burden in adults with 

 regardless of their baseline lung function and fractional exhaled nitric oxide (FeNO) scores, according to new data from the phase 4 VESTIGE trial.

American College of Chest Physicians (CHEST) 2025 Annual Meeting

 in Chicago, IL, this week, investigators from VESTIGE reported significantly reduced mucus plug scores and volume from baseline among adult patients with asthma following 24 weeks of dupilumab add-on therapy. The significant benefit was achieved irrespective of patients’ baseline pre-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV

The findings add weight to the prior VESTIGE trial evidence supporting the interleukin 4 and 13 (IL-4, IL-13) targeting biologic’s benefit to airway inflammation and mucus plugging among patients with moderate-to-severe asthma — further emboldening prescribing clinicians to consider add-on dupilumab for adult patients with moderate-to-severe type 2 asthma.

 during CHEST 2025, study author Njira Lugogo, MD, director of the University of Michigan Health’s Pulmonary & Critical Care Medicine Asthma Program, discussed the significance of achieving mucus plus burden relief in this patient population regarding of key risk biomarkers. Lugogo said mucus plugs have become an increasingly apparent issue in patients with uncontrolled asthma — though their presence and impact may still be misunderstood among her peers.

“Mucus plugs are not sputum, and they can be present in the absence of cough. So, having a productive cough does not mean you have mucus plugs, and it doesn't rule out mucus plugs. There are really no diagnostic tools in terms of patient-reported outcome measures that will tell you who has plugs and who doesn't have plugs. You actually have to look for them on imaging, and you need CT imaging to find plugging. The classical way that they measure mucus plugs is that they do a CT and then they look at the CT and count the number of sub-segmental airways that are occluded completely. You get a count of one for each occluded airway — the maximum count is 20 — and it requires a pretty onerous process where two radiologists are reading the CT and figuring out what the plugs are the counts.”

Mucus plugs are highly common in cases of type 2 asthma, and are a consequence of airway mucin MUC5AC cross-linked with Charcot-Leyden crystals (CLCs) and eosinophils producing inflammatory peroxidases that result in “very thick concretion that’s tethered to the airway.”

“They don't respond to inhaled steroids, oral steroids, nor bronchodilators. So, all our current conventional treatments do not get rid of plugs,” Lugogo said.” They make people have lower lung function. You get more air trapping. So, they do have clinical consequences for our patients, and in the context of asthma, about half the patients have mucus plugs.”

Lugogo’s advice for clinicians based on her team’s latest VESTIGE findings is to more formally adopt strategies to identify mucus plugs in patients not improving from their type 2 asthma. Initiating dupilumab has shown these patients can achieve benefit within 4 weeks.

“There's a little more improvement by 26 weeks, but it's a pretty rapid depletion improvement in plugs,” Lugogo said. “And so, you can talk to your patients about this topic, show them the plugs, and let them know with some confidence that if they have plugs, there is likely to be a clinical impact on mucus plug scores, and consequently we would expect improvements in obstruction, symptoms, and so forth.”

Lugogo additionally discussed ongoing research into artificial intelligence (AI) and machine learning to assist in automating mucus plug counting, given the time-laden standard currently at practice. The ultimate goal, she hypothesized, would be to receive automated mucus plug scores post-scan.

“There’s more to come on this topic,” Lugogo said. “I think it's going to continue to grow in terms of interest and in our ability to increase the clinical applicability of mucus plugs.”

Perez De Llano L, Dunican E, Lugogo NL, et al. Dupilumab Reduces Mucus Burden Irrespective of Baseline Respiratory Characteristics in Patients with Uncontrolled Moderate-to-Severe Asthma: Results from the VESTIGE Study. Poster presented at: CHEST Annual Meeting 2025. Chicago, IL. October 19 – 22, 2025.

Castro M, Papi A, Porsbjerg C, et al. Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial. 

. 2025;13(3):208-220. doi:10.1016/S2213-2600(24)00362-X

Njira Lugogo, MD

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