PulmPEEPs

Today we have another Pulm PEEPs Pearls episode about a core critical care topic. Furf and Monty will be giving a high level overview of the use of steroids in sepsis including a review of the relevant literature and recent guidelines, and pragmatic bedside points.

Contributors

This episode was prepared with research by Pulm PEEPs Associate Editor George Doumat.

Dustin Latimer, another Pulm PEEPs Associate Editor, assisted with audio and video editing.

Key Learning Points

Why Steroids in Sepsis?

Steroids do not treat the infection — antimicrobials are always first and remain the cornerstone. The goal is addressing critical illness–related corticosteroid insufficiency (CIRCI), where cortisol production cannot keep up with the overwhelming inflammatory demand of septic shock.

Hydrocortisone helps in two main ways:

Blunts the dysregulated inflammatory response — tempers the excessive vasodilation and febrile response that drive harm beyond the infection itself.

Restores vascular sensitivity to catecholamines — sepsis downregulates adrenergic receptors; steroids turn that responsiveness back on.

Clinical takeaway: The first thing you notice is vasopressor weaning (or a bend in the escalation curve) — not a rapid improvement in fever or white count.

Caveat: These trials predate modern sepsis phenotyping. None distinguish hyperinflammatory vs. hypoinflammatory responders — they treat all comers.

The Evidence: Four Landmark Trials

Every IM resident and critical care fellow will eventually journal-club these four. The most consistent signal across all of them is faster shock reversal and reduced vasopressor use; the mortality question remains unsettled.

Trial (Year)NRegimenKey FindingAnnane (2002)~300Hydrocortisone + fludrocortisoneMortality benefit in ACTH non-responders; criticized methodology and messy cortisol-response testing; not cleanly replicated.CORTICUS (2008)~500Hydrocortisone aloneFaster shock reversal but no mortality benefit, regardless of cortisol responsiveness. Raised (later allayed) superinfection concern. Cornerstone for abandoning routine cort-stim testing.ADRENAL (2018)~3,800Hydrocortisone aloneFaster vasopressor weaning; no 90-day mortality benefit.APROCCHSS (2018)~1,200Hydrocortisone + fludrocortisoneMortality benefit at 90 days.

Bottom line: Faster shock reversal is consistent. Mortality benefit appears in 2 of 4 trials (both used fludrocortisone) but not the others. A 2026 meta-analysis showed benefit for hydrocortisone + fludrocortisone vs. placebo, but

not for hydrocortisone + fludrocortisone vs. hydrocortisone alone — suggesting hydrocortisone drives the main effect.

Who Gets Steroids, and When?

2021 Surviving Sepsis: Consider steroids for norepinephrine or epinephrine ≥ 0.25 mcg/kg/min for ≥ 4 hours despite adequate resuscitation — a reasonable bedside trigger.

Early 2026 update: Moved away from a specific numeric trigger — consider steroids when a septic patient is not responding well to vasopressors or has escalating requirements. Make a clinical decision. (Quality of evidence: low to moderate.)

Go faster than the threshold when: Known/suspected adrenal insufficiency or home steroids, or florid pressor-requiring shock on arrival.

A practical escalation sequence: escalating norepinephrine → add vasopressin (per VASST) → then add steroids if requirements keep climbing.

Do NOT wait for an ACTH stimulation test. It does not reliably predict who responds and only delays treatment. Sepsis is an elevated-cortisol state but can dissociate ACTH and cortisol, and cortisol-binding globulin is depleted — the test is too messy to guide care.

What to Give: The Regimen

Standard dose: Hydrocortisone 200 mg/day, typically 50 mg IV Q6H. (Original trials often used continuous infusions, rarely used in the U.S.) Some start with a 100 mg bolus to gain control.

Higher dose: If chronically on steroids / adrenally insufficient, consider ~300 mg/day (e.g., 100 mg Q8H).

Fludrocortisone: Unsettled. The two mortality-benefit trials added it (50 mcg PO/NG/OG daily), but hydrocortisone already has mineralocorticoid activity and meta-analyses don’t show added benefit over hydrocortisone alone. Most clinicians omit it — adding it is reasonable and safe, just be honest about the uncertainty.

Duration & Tapering

Typical course: ~7 days is most common. Trial practices varied (ADRENAL ~7 days; VANISH used a taper after 6 days; some continue until pressors are off).

No taper needed. You do not need to taper for adrenal insufficiency after a short course — just stop. If pressors dramatically rebound, you can restart, but most patients have gained the benefit they’ll get by day 7.

Pitfalls & Safety

Hyperglycemia: Expected and must be managed (monitor closely; insulin drip if needed). No signal for major DKA / severe complications in the trials.

Superinfection / fungal infection: The most-quoted concern, but the overall literature does not show a convincing, statistically significant increase. Be disciplined about stopping on schedule.

Muscle weakness: Steroids can worsen critical illness myopathy; a short 7-day course likely has limited effect, but be aware.

Other: GI bleeding (follow general PPI prophylaxis guidance) and sodium disturbances (watch for hyper-/hyponatremia).

Two things we know: (1) steroids shorten duration of vasopressor support, and (2) they are relatively safe in sepsis. Whether they improve mortality — and in whom — remains open.

The Five Pulm PEEPs Pearls

Mechanism: Steroids restore catecholamine vascular sensitivity and blunt dysregulated inflammation. The clinical target is vasopressor weaning, not infection treatment.

Evidence: Faster shock reversal is the most consistent finding. Mortality benefit is seen in 2 of 4 trials but not the others — still controversial. Some patients likely benefit; we don’t yet know who.

Trigger: A practical 2021 threshold is levo/epi ≥ 0.25 mcg/kg/min for ≥ 4 hours. Newer guidance drops the strict number — make a clinical decision based on poor pressor response or escalation.

Dose: Hydrocortisone 200 mg/day (e.g., 50 mg Q6H). Adding fludrocortisone mirrors two trials, but meta-analyses find no benefit over hydrocortisone alone.

Safety: Steroids appear safe in sepsis. Monitor and treat hyperglycemia; no marked increase in superinfection.

References and Further Reading

Annane, Djillali et al. “Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.” JAMA vol. 288,7 (2002): 862-71. doi:10.1001/jama.288.7.862

Sprung, Charles L et al. “Hydrocortisone therapy for patients with septic shock.” The New England journal of medicine vol. 358,2 (2008): 111-24. doi:10.1056/NEJMoa071366

Venkatesh, Balasubramanian et al. “Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.” The New England journal of medicine vol. 378,9 (2018): 797-808. doi:10.1056/NEJMoa1705835

Annane, Djillali et al. “Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.” The New England journal of medicine vol. 378,9 (2018): 809-818. doi:10.1056/NEJMoa1705716

Sun, Alin et al. “Correction: Hydrocortisone combined with fludrocortisone for treatment of adults with septic shock: an updated meta-analysis and systematic review.” Frontiers in medicine vol. 13 1811616. 2 Mar. 2026, doi:10.3389/fmed.2026.1811616

Prescott, Hallie C et al. “Executive Summary: Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026.” Critical care medicine vol. 54,4 (2026): 715-724. doi:10.1097/CCM.0000000000007089

Episode Transcript

Hey everyone, Dave Furfaro here from Pulm PEEPs. As you may have noticed in the last few weeks and months, we’ve had a little bit of a decrease in the content that we’ve been putting out, and I just wanted to share a couple things with you about why that is and the future of Pulm PEEPs coming up. In December of 2025, I was diagnosed with a large myxoid liposarcoma in my leg, and since then, I have been undergoing treatment for that.

Overall, treatment has been going well, but it’s certainly been a long road that, continues, and I hope that it continues to trend positively. Kristina has been an unbelievable support during this. We have continued to work on some content as a great way and distraction for me at times, but we haven’t been able to keep up the same pace of content that we usually put out. And given everything that is going on, I actually anticipate that will continue for a few months. Ee haven’t said anything so far yet because we were still figuring it out ourselves, but now we just wanted you all to know that, we, love doing Pulm PEEPs. We’re very committed to it. We wanna get back to doing it as consistently as we have been previously, and we plan on doing that, but it likely will be a little bit of time, and this is why.

I also may be sharing more about my journey through the medical system as a patient, in the future, but for now, I’m really just focusing on my treatment, my health, and my family. So the summer months will likely be, much slower, maybe even a break off together, and look forward to recovering and getting back to producing more regular Pulm PEEPs content in the Fall.

Hope everybody who’s listening is doing well. Thank you all, as always, for being supportive, for listening to the podcast, for reaching out to us on social media, for saying hi to us in person at conferences. It’s been, a true delight, and we can’t wait to get back to business as usual. Okay, everybody. Take good care of patients, be safe, be well, and we’ll see you soon.

We’re excited today to launch our first episode in collaboration with the Irish Thoracic Society and their podcast series. The Irish Thoracic Society represents respiratory professionals throughout Ireland and is dedicated to championing excellence in the prevention, diagnosis, and clinical care of respiratory disease through its work in advocacy, education and research.

In today’s episode, we explore the complex and often overlooked world of refractory chronic cough — a condition that can significantly impact patients’ quality of life but is frequently misunderstood or underdiagnosed. With insights from leading respiratory specialists in Ireland and the United States, we discuss the latest thinking on diagnosis, management, and emerging treatments aimed at improving outcomes for patients and helping clinicians navigate this challenging area of respiratory medicine.

Joining us are renowned experts Professor Lorcan McGarvey and Professor Brendan Canning, both internationally recognised leaders in respiratory medicine and cough research. Together, they share their perspectives on the neurobiology of chronic cough, the considerable morbidity experienced by patients, and how clinicians can approach diagnostic investigations more effectively.

We also explore current treatment strategies and promising new therapies on the horizon as chronic cough increasingly gains recognition as a disease in its own right — rather than simply a symptom. Whether you’re a clinician, researcher, or simply interested in advances in respiratory medicine, this episode offers valuable insights into a condition that is finally receiving the attention it deserves.

Meet Our Co-Hosts

Marissa O’Callaghan is an Irish trained Respiratory fellow currently undertaking a post-doc fellow working in Erasmus MC Rotterdam in the Netherlands. She finished her Irish respiratory and Internal medicine training and Phd in 2025. Her areas of interest are interstitial and rare lung diseases. She enjoys clinical research, Med Ed, and dreaming up new medical innovations. Together with cohost Sandra Green, she founded the ITS podcast series in June 2024. Marissa O’Callaghan –LinkedIn

Sandra Green is an Irish-trained respiratory fellow with a strong track record in climate advocacy and multidisciplinary sustainable initiatives, as co-founder of Irish Doctors for the Environment. She has an MSc in Leadership and Innovation in Healthcare at the Royal College of Surgeons Ireland (2023–2025). With Marisssa, she co-founded the Irish Thoracic Society Podcast Productions, launching the platform in 2024 to share knowledge, insights, and innovations in respiratory care. Sandra Green – LinkedIn

Meet Our Guests

Lorcan McGarvey is a professor of respiratory medicine at the University of Belfast, with a focus on the neurobiology of cough. His research has significantly contributed to the understanding of cough hypersensitivity syndrome and the development of new therapeutic strategies. Lorcan is a respected voice in the field, known for his collaborative work and dedication to advancing respiratory health.

Brendan Canning is a distinguished researcher at Johns Hopkins University, specializing in the mechanisms of cough and airway diseases. His pioneering studies on neural pathways and receptor targets have paved the way for novel treatments in refractory chronic cough. Brendan’s expertise and innovative approach make him a key figure in the ongoing efforts to redefine chronic cough management.

In This Episode

The definitions and classifications of chronic cough, including unexplained, refractory, and unexplained refractory cough

The importance of a thorough clinical history and focused diagnostics over exhaustive testing

Common causes of chronic cough

The role of personalized, multidisciplinary management—combining pharmacologic, speech therapy, and psychological support—to improve quality of life for even the most challenging patients.

The concept of cough hypersensitivity syndrome and its role in refractory cases

Evidence-based approach to treatment, including pharmacologic and non-pharmacologic options

Emerging therapies on the horizon, including novel receptor modulators and neuromodulatory agents and ongoing clinical trials in this rapidly evolving field

The impact of chronic cough on mental health, social life, and overall quality of life

The importance of reframing chronic cough as a disease entity in its own right

References and Further Reading

Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008;371(9621):1364-1374.

Gibson PG, Vertigan AE. Management of chronic refractory cough. BMJ. 2015;351:h5590.

Matsumoto H, Kanemitsu Y, Ohe M, Tanaka H, Terada K, Nishi K, et al. Real-world usage and response to gefapixant in refractory chronic cough. ERJ Open Res. 2025;11(4):01037-2024. doi:10.1183/23120541.01037-2024.

McGarvey LP, Birring SS. Cough hypersensitivity syndrome: a novel paradigm for understanding cough. Lancet Respir Med. 2014;2(8):647-656.

Morice AH, Millqvist E, Bieksiene K, Birring SS, Dicpinigaitis P, Ribas CD, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J. 2020;55(1):1901136.

Parker SM, Smith JA, Birring SS, Chamberlain-Mitchell S, Gruffydd-Jones K, Haines J, et al. British Thoracic Society clinical statement on chronic cough in adults. Thorax. 2023;78(Suppl 1):S3-S19.

Smith JA, Woodcock A. Chronic cough. N Engl J Med. 2006;354(2):136-144.

Song WJ, Dupont L, Birring SS, Chung KF, Dąbrowska M, Dicpinigaitis P, et al. Consensus goals and standards for specialist cough clinics: the NEUROCOUGH international Delphi study. ERJ Open Res. 2023;9(6):00618-2023. doi:10.1183/23120541.00618-2023.

Song WJ, McGarvey L, Cho PSP, Mazzone SB, Chung KF, editors. Chronic cough. Sheffield: European Respiratory Society; 2025.

We are unbelievably excited this week to be reviewing the hot-off-the-presses 2026 Multi-Society (AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN) Pulmonary Embolism Guidelines with lead author Dr. Mark A. Creager. We will talk about key updates in these guidelines compared to prior practice, including the new risk classification model, and provide an overview from diagnosis to follow-up. Given the clinical importance and prevalence of pulmonary embolism, these guidelines are certainly going to shape practice going forward, so this episode is a can’t miss!

Watch the full video of this episode with graphics and helpful teaching visuals on our YouTube channel: https://www.youtube.com/@pulmpeeps

Meet Our Guest

Dr. Mark Creager is a Professor of Medicine at Dartmouth Hitchcock Medical Center where he specializes in Cardiovascular Medicine with an emphasis on venous thromboembolic disease. He served as the lead author of the 2026 Pulmonary Embolism Guidelines.

Article and Reference

Creager MA, Barnes GD, Giri J, Mukherjee D, Jones WS, Burnett AE, Carman T, Casanegra AI, Castellucci LA, Clark SM, Cushman M, de Wit K, Eaves JM, Fang MC, Goldberg JB, Henkin S, Johnston-Cox H, Kadavath S, Kadian-Dodov D, Keeling WB, Klein AJP, Li J, McDaniel MC, Moores LK, Piazza G, Prenger KS, Pugliese SC, Ranade M, Rosovsky RP, Russo F, Secemsky EA, Sista AK, Tefera L, Weinberg I, Westafer LM, Young MN. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026 Feb 19:S0735-1097(25)10161-7. doi: 10.1016/j.jacc.2025.11.005. Epub ahead of print. PMID: 41712898.

Key Learning Points

Why these guidelines matter:

This is the first joint AHA/ACC clinical practice guideline specifically on acute PE, bringing together a truly multidisciplinary writing committee (cardiology, pulmonology, hematology, emergency medicine, interventional radiology, surgery, and others). Prior guidelines existed from individual societies, but nothing this comprehensive had been updated in roughly five to six years.

New PE clinical categories (A through E):

One of the most impactful changes is replacing the old “massive/submassive” and “low/intermediate/high risk” labels with five categories that form a severity continuum. Category A is subclinical (incidental PE found on imaging in asymptomatic patients). Category B covers symptomatic but low-severity patients. Category C is where much of the clinical complexity lives — symptomatic, hemodynamically stable patients subdivided into C1, C2, and C3 based on RV function and biomarkers. Category D represents incipient cardiopulmonary failure (transient hypotension, normotensive shock with end-organ dysfunction). Category E is frank cardiopulmonary failure, with E2 being the sickest — refractory or recurrent cardiac arrest. Respiratory modifiers (hypoxia requiring supplemental oxygen) layer onto C, D, and E.

Diagnostic approach:

Clinical evaluation comes first — history, exam, and validated decision tools (Wells score, revised Geneva, PERC). If clinical probability is low and D-dimer is normal, imaging can be safely avoided. If either is concerning, imaging is warranted. CTPA remains the preferred imaging modality due to superior sensitivity, specificity, wide availability, and ability to assess clot burden and alternative diagnoses. VQ scanning is still appropriate when CTPA is contraindicated, and VQ SPECT offers better reproducibility and specificity than traditional planar VQ if available. Echocardiography is not a diagnostic test for PE but is important for risk stratification — RV size, TAPSE, and tissue Doppler measures all contribute prognostic information.

Anticoagulation updates:

Anticoagulation remains the cornerstone of treatment. For patients potentially needing advanced therapies (C3, D, E), parenteral anticoagulation is started first. A notable recommendation: low molecular weight heparin is generally preferred over unfractionated heparin, based on evidence showing more effective VTE risk reduction, more predictable pharmacokinetics, no need for routine monitoring, lower rates of heparin-induced thrombocytopenia, and no increase in major bleeding. The committee acknowledged this may create discomfort for clinicians accustomed to unfractionated heparin’s easy reversibility, but the difficulty of achieving and maintaining therapeutic levels with UFH was a significant concern.

Advanced therapies:

Catheter-based thrombolysis, mechanical thrombectomy, systemic thrombolysis, and surgical embolectomy all received mostly class 2B recommendations (“can consider”) for C3 and D categories, reflecting that current evidence shows improvement in short-term surrogate measures (RV/LV ratio, hemodynamics) but lacks definitive hard outcome data on mortality. For category E1 patients, recommendations are stronger (class 2A). Multiple trials are expected soon — HI-PEITHO, PEERLESS-2, PE-TRACT, PERSEVERE, TORPEDO, and PROG — that should substantially inform future updates.

PERT teams:

Pulmonary embolism response teams are encouraged, particularly for C3, D, and E patients. They’ve been shown to reduce length of stay. For institutions without PERT capability, establishing consultation networks with larger centers is recommended.

Post-PE follow-up:

Patients shouldn’t be “left in the wilderness” after discharge. The guidelines recommend communication within the first week to ensure understanding of diagnosis and treatment, an in-person visit at or before three months to assess for persistent symptoms and discuss anticoagulation duration, ongoing surveillance for chronic thromboembolic pulmonary disease, and periodic reassessment for those on extended anticoagulation.

Infographics

Furf and Monty are back with another Pulm PEEPs Pearls episode. The topic of today’s discussion is an often discussed, but often misunderstood, test; the methacholine challenge. They’ll review when to utilize this test, how it should be performed, and the appropriate interpretation.

Contributors

This episode was prepared with research by Pulm PEEPs Associate Editor George Doumat.

Dustin Latimer, another Pulm PEEPs Associate Editor, assisted with audio and video editing.

Key Learning Points

What the Test Measures

Methacholine challenge is a direct bronchial provocation test of airway hyperresponsiveness (AHR), a core physiologic feature of asthma.

Anyone will bronchoconstrict at high enough concentrations — the test looks for an abnormal threshold.

The key endpoint is the PC20: the methacholine concentration causing a 20% fall in FEV1.

Abnormal in adults: PC20 ≤ 8–16 mg/mL

Test Performance

Meta-analyses: pooled sensitivity ~60%, specificity ~90%.

Real-world cohorts: sensitivity 55–62%, specificity 56–100% (varies by population, protocol, and threshold used).

Not a standalone yes/no test — best used as part of a broader diagnostic pathway.

Where It Fits in the Asthma Workup

The test belongs in a stepwise approach:

Step 1: Spirometry + bronchodilator response

Step 2: Add FeNO and/or peak flow variability (if available)

Step 3: If the picture is still unclear → methacholine challenge

It is most useful for symptomatic patients with normal spirometry and no bronchodilator reversibility. Given its cost, mild risk, and discomfort, it should not be a first-line test — most asthma diagnoses do not require it.

Technique and Medication Prep

Technique

ERS guidelines favor tidal breathing over deep inspiratory maneuvers.

Deep breaths can be bronchoprotective and blunt the response, reducing sensitivity — especially in mild or well-controlled asthma.

Medication Washout (to Avoid False Negatives)

Medication ClassWashout PeriodShort-acting beta-agonists (SABA)≥ 6 hoursLong-acting beta-agonists (LABA)~24 hoursUltra-long-acting beta-agonists~48 hoursShort-acting anticholinergics (e.g., ipratropium)~12 hoursLong-acting muscarinic antagonists (LAMA, e.g., tiotropium)7 days

Inhaled corticosteroids, leukotriene blockers, and antihistamines do not significantly affect the test acutely — continue these. Withdrawing ICS also carries its own risk for asthma patients.

Practical tip: Spell out exactly what to hold and when — for both the patient and the PFT lab — at the time the test is ordered.

Interpreting Results

Negative Test (PC20 > 16 mg/mL)

Very high negative predictive value in symptomatic adults.

Makes current asthma quite unlikely (assuming proper test conduct).

This is the test’s greatest strength: it is an excellent rule-out test.

Positive Test (PC20 ≤ 8–16 mg/mL)

More nuanced — airway hyperresponsiveness is not unique to asthma.

Can be positive in: chronic cough, allergic rhinitis, COPD, and even some healthy asymptomatic individuals.

A positive result raises probability but must be interpreted alongside the clinical story, variable respiratory symptoms, peak flow variability, FeNO, and ICS response.

Safety and Risks

Overall, the test is quite safe; significant adverse effects are rare.

Temporary breathing discomfort is expected (bronchoconstriction is being induced).

Severe bronchospasm is possible:

A trained clinician should be available; SABA inhaler/nebulizer must be immediately on hand; a physician should be reachable in the facility.

Contraindications / cautions:

Avoid if FEV1 < 70% predicted or < 1–1.5 L (baseline obstruction greatly increases risk).

Avoid within 3 months of an acute cardiac event (rare risk of cardiac events with unstable cardiac disease).

Five Pearls — Quick Recap

What it tests: Methacholine challenge is a direct test of AHR with high specificity but variable sensitivity — it belongs inside a diagnostic pathway, not as a standalone asthma test.

When to use it: Most useful for symptomatic patients with normal spirometry and no bronchodilator response, after FeNO and peak flow variability have been considered.

Technique and meds matter: Use tidal breathing protocol; respect washout intervals — especially the 7-day LAMA washout and 24–48 hour LABA window — to avoid false negatives.

Safety: Generally safe, but can induce significant bronchoconstriction. Have a SABA available and avoid the test in patients with FEV1 < 70% predicted.

Interpretation: A negative test (PC20 > 16 mg/mL) strongly argues against current asthma. A positive test raises probability but is not specific — interpret alongside the full clinical picture.

References and Further Reading

Coates AL, Wanger J, Cockcroft DW, Culver BH; Bronchoprovocation Testing Task Force: Kai-Håkon Carlsen; Diamant Z, Gauvreau G, Hall GL, Hallstrand TS, Horvath I, de Jongh FHC, Joos G, Kaminsky DA, Laube BL, Leuppi JD, Sterk PJ. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests. Eur Respir J. 2017 May 1;49(5):1601526. doi: 10.1183/13993003.01526-2016. PMID: 28461290.

Lee, J., & Song, J. U. (2021). Diagnostic comparison of methacholine and mannitol bronchial challenge tests for identifying bronchial hyperresponsiveness in asthma: a systematic review and meta-analysis. Journal of Asthma, 58(7), 883–891. https://doi.org/10.1080/02770903.2020.1739704

Davis BE, Blais CM, Cockcroft DW. Methacholine challenge testing: comparative pharmacology. J Asthma Allergy. 2018 May 14;11:89-99. doi: 10.2147/JAA.S160607. PMID: 29785128; PMCID: PMC5957064.