Inhaled corticosteroids (ICS) are the cornerstone of asthma controller therapy and have a more limited but real role in COPD (chronic obstructive pulmonary disease). Understanding why ICS produce more consistent and dramatic benefit in asthma than in COPD requires understanding the fundamental differences in airway inflammatory phenotype between the two diseases. Those differences are mechanistic, not merely quantitative, and they predict both efficacy and adverse effect risk with striking accuracy.
Asthma is predominantly a disease of eosinophilic airway inflammation driven by the type 2 (T2) immune response. In response to inhaled allergens or other triggers, airway epithelial cells release the cytokines interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP), which activate type 2 innate lymphoid cells (ILC2s) and antigen-presenting dendritic cells. ILC2s produce large quantities of interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) independent of antigen stimulation, amplifying the T2 response. IL-4 and IL-13 drive the differentiation of naive T helper cells (Th0) toward the Th2 phenotype; IL-5 is the principal cytokine responsible for eosinophil maturation, recruitment, and survival; and IL-13 drives airway smooth muscle hyperresponsiveness, goblet cell metaplasia, and subepithelial fibrosis.1 Mast cells, degranulating in response to allergen-IgE crosslinking on their surface, release histamine, cysteinyl leukotrienes, and prostaglandin D2, producing acute bronchoconstriction and contributing to chronic airway remodeling.12
ICS suppress eosinophilic airway inflammation through multiple glucocorticoid receptor (GR)-mediated mechanisms. They reduce transcription of genes encoding Th2 cytokines (IL-4, IL-5, IL-13), suppress ILC2 activity, impair eosinophil survival and adhesion molecule expression, stabilize mast cells, and reduce mucus hypersecretion by down-regulating goblet cell hyperplasia. Because the T2 immune response is cytokine-driven and glucocorticoid-sensitive at its core, ICS produce large, consistent reductions in eosinophilic airway inflammation, exacerbation frequency, and bronchial hyperresponsiveness in asthma. This mechanistic targeting explains why ICS are first-line controller therapy for all but the mildest asthma.1
COPD is driven by a distinctly different inflammatory process, primarily neutrophilic rather than eosinophilic, and dominated by the innate immune response to cigarette smoke and other noxious particles. The characteristic cellular infiltrate of COPD includes neutrophils, macrophages, and CD8-positive cytotoxic T lymphocytes, with relative paucity of eosinophils in most patients. Neutrophilic inflammation is driven by IL-8 (CXCL8), leukotriene B4 (LTB4), and tumor necrosis factor-alpha (TNF-alpha); it is far less sensitive to glucocorticoids than the Th2/eosinophilic response, because neutrophil survival and recruitment are not primarily cytokine-dependent in the same way eosinophil survival is.2 Macrophage-driven proteolytic destruction of the alveolar-capillary unit by matrix metalloproteinases (MMPs) and neutrophil elastase underlies emphysema and is also glucocorticoid-resistant. This mechanistic explanation predicts and explains the consistently smaller effect size of ICS in COPD compared with asthma.
A clinically important subset of COPD patients does have elevated blood and airway eosinophils, and this subgroup derives substantially greater benefit from ICS than patients with purely neutrophilic disease. Blood eosinophil count has emerged as the most practical biomarker for predicting ICS benefit in COPD: patients with blood eosinophils of 300 cells per microliter or higher derive the most consistent exacerbation-reduction benefit from ICS-containing regimens, while those with counts below 100 cells per microliter derive little if any benefit and face the same ICS-associated risks.3 This eosinophil threshold-guided approach is now embedded in the GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2024 treatment algorithm for triple therapy decisions. The concept of T2-high versus T2-low disease cuts across the asthma-COPD diagnostic boundary: T2-high patients (high eosinophils, high IgE or FeNO [fractional exhaled nitric oxide]) respond to ICS and to biologic agents targeting the T2 pathway regardless of the spirometric diagnosis; T2-low patients (neutrophilic, low eosinophils) respond poorly to ICS and are better managed with bronchodilators alone.
Blood eosinophil count above 300 cells per microliter and fractional exhaled nitric oxide (FeNO) above 25 parts per billion (ppb) are the most accessible T2-high markers in clinical practice. Elevated serum IgE supports allergic T2 disease. In practice, a patient with asthma-like symptoms, blood eosinophils above 300 cells per microliter, and FeNO above 25 ppb is virtually certain to have T2-high disease and will respond robustly to ICS. A patient with COPD, low eosinophils, and heavy smoking history is T2-low and should receive bronchodilator therapy; adding ICS provides incremental pneumonia risk without proportionate benefit.
All inhaled corticosteroids (ICS) act through the glucocorticoid receptor (GR), a cytoplasmic nuclear receptor that, upon ligand binding, translocates to the nucleus to regulate gene transcription. Despite sharing this fundamental mechanism, ICS agents differ substantially in receptor binding affinity, lipophilicity, pulmonary deposition, systemic bioavailability after first-pass metabolism, and local airway residence time. These pharmacological differences translate into clinically meaningful differences in efficacy-to-safety ratio across the available agents.
The glucocorticoid receptor exists in two principal isoforms produced by alternative splicing: GR-alpha and GR-beta. GR-alpha is the classical ligand-binding receptor responsible for anti-inflammatory gene regulation. GR-beta does not bind glucocorticoids and acts as a dominant-negative inhibitor of GR-alpha; its overexpression contributes to glucocorticoid resistance in severe asthma and in COPD (chronic obstructive pulmonary disease). Upon ICS binding to GR-alpha, the receptor dissociates from heat shock protein complexes, dimerizes, and translocates to the nucleus. The major anti-inflammatory effects of ICS occur through two nuclear mechanisms. Transrepression involves GR monomer interaction with pro-inflammatory transcription factors, particularly nuclear factor-kappa B (NF-kB) and activator protein-1 (AP-1), inhibiting their ability to drive cytokine gene transcription, which accounts for most anti-inflammatory benefit. Transactivation involves GR dimer binding to glucocorticoid response elements (GREs) in gene promoters, inducing expression of anti-inflammatory proteins such as lipocortin-1 (annexin A1), mitogen-activated protein kinase phosphatase-1 (MKP-1), and secretory leukoprotease inhibitor (SLPI).1 Systemic adverse effects of glucocorticoids arise predominantly through transactivation, because genes for glucose metabolism, bone density regulation, skin thinning, and hypothalamic-pituitary-adrenal (HPA) axis suppression are GRE-driven. This distinction has prompted efforts to develop GR ligands with selective transrepression over transactivation activity, though none have reached clinical use at the time of this writing.
Lipophilicity is the most pharmacologically consequential physicochemical property differentiating ICS agents. Highly lipophilic ICS dissolve into airway epithelial cell membranes and form intracellular lipid depots, creating a local reservoir that sustains prolonged GR occupancy without requiring continuously high free drug concentrations in airway lining fluid. Fluticasone propionate and fluticasone furoate are among the most lipophilic ICS in clinical use; their high lipophilicity explains their prolonged duration of effect with once-daily (fluticasone furoate) or twice-daily (fluticasone propionate) dosing. Budesonide has intermediate lipophilicity and forms reversible fatty acid conjugates within airway cells, a form of local retention distinct from simple lipid dissolution. Beclomethasone dipropionate is a prodrug that is converted to the active form beclomethasone-17-monopropionate (17-BMP) by airway esterases; 17-BMP has high GR binding affinity and contributes to beclomethasone's efficacy at relatively low nominal doses. Ciclesonide is also a prodrug activated to des-ciclesonide by airway esterases, with minimal GR affinity until conversion occurs, which theoretically reduces oropharyngeal deposition effects because activation occurs primarily in the lower airways.2
Systemic bioavailability of swallowed ICS, reflecting oropharyngeal deposition, is a major determinant of systemic adverse effect risk. After inhalation, a fraction of drug deposits in the oropharynx, is swallowed, reaches the gastrointestinal tract, is absorbed, and must survive first-pass hepatic metabolism before reaching the systemic circulation. ICS with high first-pass extraction ratios (fluticasone propionate approximately 99%, budesonide approximately 90%) have low systemic bioavailability from swallowed drug, making oropharyngeal deposition less consequential for systemic adverse effects. The inhaled fraction that deposits in the lung is absorbed directly into the pulmonary circulation, bypassing first-pass metabolism entirely. Spacer use with pMDI (pressurized metered-dose inhaler) reduces oropharyngeal deposition, reducing swallowed dose, and is therefore doubly beneficial for ICS: it improves lung deposition and reduces systemic bioavailability from GI absorption simultaneously.4
Fluticasone propionate (FP): very high GR affinity; very high lipophilicity; once or twice-daily dosing; high first-pass extraction; available in multiple fixed-dose combinations. Fluticasone furoate (FF): highest GR affinity of any commercial ICS; very high lipophilicity; once-daily dosing; available with vilanterol (Breo Ellipta) and vilanterol plus umeclidinium (Trelegy Ellipta). Budesonide: intermediate lipophilicity; reversible fatty acid conjugation for retention; approximately 90% first-pass extraction; available with formoterol as Symbicort (the ICS/LABA (long-acting beta-2 agonist combination) used in SMART (Single Maintenance And Reliever Therapy)). Beclomethasone: prodrug to 17-BMP; lower dose needed per effect; pMDI standard. Ciclesonide: prodrug activated in lower airways; reduced oropharyngeal effects; once-daily dosing; Alvesco.
Inhaled corticosteroids (ICS) carry a spectrum of adverse effects ranging from locally mediated oropharyngeal complications that are almost universal at moderate-to-high doses to systemic effects that are dose-dependent and genuinely clinically significant only at the higher dose range. Understanding the mechanisms behind each adverse effect category allows the clinician to counsel patients accurately, prevent complications with straightforward measures, and make rational decisions about when dose reduction or alternative strategies are warranted.
Oral candidiasis (oropharyngeal candidiasis, OPC) is the most common local adverse effect of ICS and results from glucocorticoid-mediated suppression of local innate and adaptive immune defenses in the oropharynx, combined with the direct local drug effect on oral flora. Topical glucocorticoids impair neutrophil and lymphocyte function at the oropharyngeal mucosa, reducing clearance of Candida albicans, which colonizes the pharynx in a significant proportion of the population. OPC presents as white plaques on the buccal mucosa, tongue, or palate, sometimes accompanied by pharyngeal soreness or dysgeusia (altered taste). Prevention is straightforward and effective: rinsing the mouth and gargling with water immediately after each ICS dose, followed by spitting (not swallowing), removes deposited drug from oropharyngeal surfaces and substantially reduces OPC incidence. Spacer use further reduces oropharyngeal deposition. Established OPC is treated with topical antifungal agents such as clotrimazole troches or nystatin suspension; persistent or severe cases may require oral fluconazole.4
Dysphonia (hoarseness) is a second common local adverse effect, affecting up to 30% of patients on regular ICS therapy. The mechanism differs from OPC: dysphonia results from glucocorticoid-induced myopathy of the intrinsic laryngeal muscles, particularly the posterior cricoarytenoid muscles that abduct the vocal cords, combined with local deposition of drug on the laryngeal mucosa. The result is imprecise vocal cord adduction, producing a rough, breathy, or hoarse voice quality. Dysphonia is particularly problematic for professional voice users such as teachers, singers, and performers. Management includes dose reduction if clinically feasible, switching to a spacer with pMDI (pressurized metered-dose inhaler) devices, and considering ciclesonide (with its lower oropharyngeal deposition) in susceptible patients. Unlike OPC, dysphonia does not respond reliably to oropharyngeal rinsing because the laryngeal myopathy component is not prevented by removing surface drug deposits.4
Hypothalamic-pituitary-adrenal (HPA) axis suppression is the most clinically significant systemic adverse effect of ICS and occurs when systemically absorbed ICS suppress corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) secretion, reducing endogenous cortisol production. The degree of HPA suppression is dose-dependent and is influenced by the systemic bioavailability of the specific ICS agent, the delivery device, and patient factors including body size and concurrent use of potent CYP3A4 inhibitors (which increase ICS plasma concentrations by impairing hepatic clearance). At standard low-to-medium doses used in step 2 to step 3 asthma therapy, HPA suppression is generally subclinical. At high doses, particularly above the equivalent of 1000 micrograms per day of fluticasone propionate, clinically significant HPA suppression may occur, and patients who have been on high-dose ICS long-term are at risk for secondary adrenal insufficiency if ICS is abruptly discontinued or during physiological stress such as surgery or major illness.4
Bone mineral density (BMD) reduction is a dose-dependent long-term effect of ICS that has been demonstrated in several observational studies and meta-analyses. Glucocorticoids reduce BMD through multiple mechanisms: impaired osteoblast proliferation and function, increased osteoclast activity, reduced intestinal calcium absorption, and increased urinary calcium excretion. The magnitude of BMD reduction with ICS at standard doses is substantially smaller than with equivalent doses of systemic corticosteroids, but it is not zero. Patients on high-dose ICS for prolonged periods, particularly postmenopausal women and older men who already have low baseline BMD, should have BMD monitored and should receive supplemental calcium and vitamin D.4 The risk of clinical fractures from ICS at standard doses is debated in the literature; the evidence is stronger for hip fracture risk at high ICS doses.
Growth suppression in children treated with ICS has been demonstrated in controlled trials, most convincingly in a long-term follow-up of the Childhood Asthma Management Program (CAMP) trial, which showed a small but statistically significant reduction in adult height of approximately 1.2 centimeters in children treated with budesonide compared with placebo over the 4.5-year trial period.5 Growth effects are dose-dependent and are most pronounced in the first year of ICS therapy. The clinical context is important: uncontrolled asthma itself impairs growth, and the height deficit from ICS use must be weighed against the developmental and pulmonary consequences of inadequately treated asthma. At low-to-moderate ICS doses, the balance of benefit versus growth risk strongly favors treatment. Cataract formation (posterior subcapsular cataracts) and skin thinning (dermally applied corticosteroid effects appearing when high-dose ICS leads to sufficient systemic absorption) have been reported at high cumulative ICS doses.
Local (device-dependent, mostly preventable): oral candidiasis (treat with topical antifungals; prevent with mouth rinsing and spacer); dysphonia (dose reduction, spacer, or device switch; not reliably prevented by rinsing).
Systemic at high dose: HPA axis suppression (clinically significant above approximately 1000 mcg/day FP equivalent; risk of secondary adrenal insufficiency during physiological stress); BMD reduction (supplement calcium and vitamin D; monitor BMD in high-risk patients); growth suppression in children (dose-dependent; weigh against cost of uncontrolled asthma); posterior subcapsular cataracts; skin bruising and thinning.
Class-specific pneumonia signal: fluticasone propionate-containing combinations (FP/salmeterol) are associated with an increased pneumonia risk in COPD (chronic obstructive pulmonary disease) patients, demonstrated in the TORCH trial and multiple subsequent studies. This signal is attenuated or absent with budesonide-containing combinations. ICS should not be routinely prescribed in COPD without eosinophil guidance, partly because of this pneumonia risk.6
The pairing of ICS (inhaled corticosteroids) and LABA (long-acting beta-2 agonists) in fixed-dose combinations reflects a pharmacological relationship that is synergistic at the molecular level, not merely the convenience of co-administration. The two drug classes interact at the glucocorticoid receptor, at the beta-2 adrenergic receptor, and at shared signaling intermediates in airway smooth muscle and inflammatory cells. This molecular synergy supports superior clinical outcomes with the combination compared with either agent alone at equivalent doses, and it underpins the safety rationale for mandating that LABAs in asthma be prescribed only with concomitant ICS.
The molecular basis for ICS/LABA synergy involves reciprocal enhancement at several levels. Corticosteroids up-regulate beta-2 adrenergic receptor expression and inhibit beta-2 receptor desensitization: they increase transcription of the ADRB2 gene, increasing receptor density on airway smooth muscle, and they inhibit GRK2 (G protein receptor kinase 2)-mediated receptor phosphorylation that would otherwise promote receptor internalization and tolerance. Conversely, beta-2 agonist-induced PKA (protein kinase A) activation phosphorylates and activates GR-alpha (glucocorticoid receptor-alpha), enhancing its nuclear translocation and transcriptional activity even in the absence of additional glucocorticoid ligand. At the level of gene regulation, ICS and LABAs cooperate to suppress the same pro-inflammatory transcription factors (NF-kB [nuclear factor-kappa B], AP-1 [activator protein-1]) through overlapping but distinct mechanisms, producing greater combined suppression than either drug achieves independently.2 This synergism means that an ICS/LABA combination provides equivalent anti-inflammatory control at a lower ICS dose than ICS monotherapy, or greater control at the same ICS dose.
Fluticasone propionate/salmeterol (Advair, Wixela) was the first widely used ICS/LABA fixed-dose combination and remains available in both DPI (dry powder inhaler, Diskus) and pMDI (pressurized metered-dose inhaler) formulations. It is approved for both asthma and COPD (chronic obstructive pulmonary disease). Fluticasone propionate/formoterol fumarate (Flutiform) is a pMDI combination that pairs the high-GR-affinity ICS with the rapid-onset, full-agonist LABA. Budesonide/formoterol (Symbicort) is a pMDI and DPI combination that is uniquely suited for SMART (Single Maintenance And Reliever Therapy) strategy because formoterol's rapid onset allows it to serve as a rescue bronchodilator while budesonide provides controller ICS with each dose. Fluticasone furoate/vilanterol (Breo Ellipta) is a once-daily DPI (dry powder inhaler) combination approved for both asthma and COPD, with fluticasone furoate providing the highest GR binding affinity of any approved ICS and vilanterol providing 24-hour bronchodilation.2
The evidence base for SMART therapy with budesonide/formoterol consists primarily of the SYGMA 1, SYGMA 2, and Novel START trials. SYGMA 1 compared as-needed budesonide/formoterol versus regular budesonide (twice-daily) plus as-needed terbutaline in mild asthma over 52 weeks. As-needed budesonide/formoterol produced 64% fewer severe exacerbations than as-needed terbutaline and was superior to regular budesonide plus as-needed terbutaline for exacerbation prevention, though it was inferior to regular budesonide for symptom control as measured by the Asthma Control Questionnaire. SYGMA 2 demonstrated non-inferiority of as-needed budesonide/formoterol to regular budesonide plus as-needed terbutaline for severe exacerbation rates, with approximately one-quarter the ICS exposure in the as-needed arm.8 The Novel START trial compared as-needed budesonide/formoterol versus regular budesonide plus as-needed salbutamol (SABA, short-acting beta-2 agonist) versus as-needed salbutamol alone, demonstrating that as-needed ICS/formoterol reduced severe exacerbations compared with as-needed SABA alone. Together, these trials established that as-needed budesonide/formoterol is an effective alternative to traditional maintenance ICS therapy in mild asthma and is superior to SABA-only rescue at all disease severity levels.
SMART therapy with budesonide/formoterol requires patient education around a concept that differs from traditional inhaler regimens. In the traditional approach, maintenance and rescue inhalers are separate, with a short-acting beta-2 agonist (SABA) used for rescue and a scheduled ICS or ICS/LABA used for control. In SMART, a single inhaler serves both functions: one or two inhalations of budesonide/formoterol daily as scheduled maintenance, with additional inhalations as needed for breakthrough symptoms, with a maximum of typically eight inhalations per day. Each rescue inhalation delivers both a bronchodilator (formoterol, rapid onset) and an anti-inflammatory controller (budesonide). Patients whose rescue use increases significantly are signaled by this single inhaler to seek medical review, since increasing rescue use reflects worsening control. SMART cannot be implemented with salmeterol-containing combinations because salmeterol's slow onset makes it unsuitable as a rescue agent.
The addition of a long-acting muscarinic antagonist (LAMA) to an existing ICS (inhaled corticosteroid)/LABA (long-acting beta-2 agonist) regimen constitutes triple therapy, which represents the maximum pharmacological intensity of inhaled controller treatment currently available. In COPD (chronic obstructive pulmonary disease), triple therapy is reserved for patients with high exacerbation burden and biomarker evidence suggesting ICS responsiveness. In asthma, triple therapy with ICS/LABA/LAMA is used in step 5 severe uncontrolled disease before or alongside consideration of biologic agents. Rational use of triple therapy requires understanding both the evidence that supports it and the specific patient characteristics that predict benefit versus risk.
The IMPACT trial (Informing the Pathway of COPD Treatment) was the largest and most definitive trial of triple therapy in COPD, enrolling 10,355 patients with moderate-to-very-severe airflow obstruction and at least one moderate exacerbation or hospitalization in the prior year. Patients were randomized to fluticasone furoate/umeclidinium/vilanterol (triple therapy as Trelegy Ellipta), fluticasone furoate/vilanterol (ICS/LABA), or umeclidinium/vilanterol (LABA/LAMA). Triple therapy reduced the rate of moderate and severe exacerbations by 25% relative to LABA/LAMA and by 15% relative to ICS/LABA.9 Triple therapy also produced greater FEV1 (forced expiratory volume in 1 second) improvement than either dual combination. However, the rate of confirmed pneumonia was higher in both fluticasone furoate-containing arms (triple therapy and ICS/LABA) than in the LABA/LAMA arm, which is consistent with the class-wide pneumonia signal for ICS in COPD. The excess pneumonia risk was approximately 3 additional cases per 100 patient-years of fluticasone furoate exposure relative to LABA/LAMA, which needs to be weighed against the exacerbation reduction benefit.
The TRILOGY trial evaluated triple therapy delivered in a single inhaler (beclomethasone/formoterol/glycopyrrolate, Trimbow) versus beclomethasone/formoterol dual therapy in patients with severe COPD, demonstrating a 23% reduction in moderate-to-severe exacerbations with triple therapy.7 The extrafine particle formulation used in Trimbow achieves higher peripheral airway deposition than standard beclomethasone formulations, which may contribute to efficacy. Together with IMPACT, TRILOGY established triple therapy as the standard maximum inhaled pharmacological option for COPD patients with recurrent exacerbations despite dual bronchodilator therapy.
Blood eosinophil count is now established as the primary biomarker guiding ICS therapy decisions in COPD. The key thresholds from the GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2024 guidelines are as follows: patients with blood eosinophils of 300 cells per microliter or higher are most likely to benefit from ICS-containing regimens and should receive triple therapy if they have recurrent exacerbations on LABA/LAMA; patients with eosinophils between 100 and 300 cells per microliter may derive intermediate benefit, and ICS addition is considered on an individual basis; patients with eosinophils below 100 cells per microliter are unlikely to benefit from ICS and are at increased risk of ICS-associated pneumonia, so ICS should generally be withheld or withdrawn in this population.3 These thresholds are not absolute cutoffs but probabilistic guides; the clinical decision must also account for exacerbation frequency, severity, concurrent respiratory tract infection risk, and patient preference.
Step-up and step-down strategy in asthma follows the GINA (Global Initiative for Asthma) ladder. Step-up from step 2 (low-dose ICS as controller) to step 3 involves either doubling the ICS dose, adding a LABA as a fixed-dose ICS/LABA combination, or switching the reliever to a SMART (Single Maintenance And Reliever Therapy) regimen. The decision between doubling ICS versus adding LABA is informed by the degree of bronchodilator reversibility and patient symptom pattern; patients with predominantly bronchospastic symptoms benefit more from LABA addition, while those with predominantly inflammatory symptoms may respond better to ICS dose increase.11 Step-up to step 4 adds medium-to-high-dose ICS/LABA, and step 5 incorporates high-dose ICS/LABA with possible LAMA addition, biologic therapy referral, or low-dose oral corticosteroid (OCS). Step-down should be considered after a period of sustained asthma control of at least three months, beginning with ICS dose reduction of approximately 25 to 50% before considering removal of add-on agents.10
The pneumonia signal associated with fluticasone propionate in COPD warrants specific attention because it has direct implications for ICS selection in patients for whom ICS treatment is otherwise indicated. The TORCH trial (Towards a Revolution in COPD Health) and multiple subsequent real-world studies demonstrated a statistically significant increase in pneumonia incidence with salmeterol/fluticasone propionate compared with salmeterol alone or placebo in COPD patients, without a corresponding increase in pneumonia-related mortality. The same signal has been less consistently demonstrated with budesonide-containing combinations. The mechanism is not fully established but may relate to the deeper peripheral airway deposition of the extrafine budesonide formulations and/or pharmacokinetic differences in how the two ICS agents interact with alveolar macrophage function. When ICS is indicated in COPD patients with eosinophil counts supporting its use, the choice between fluticasone-based and budesonide-based regimens may be influenced by patient-specific pneumonia risk factors such as prior pneumonia history, low body mass index, older age, and severe airflow limitation.
Asthma step-up triggers: persistent symptoms despite current therapy, one or more severe exacerbations in the past year, reliever use more than twice weekly (excluding exercise-induced events). Before stepping up, confirm diagnosis, check inhaler technique, and assess adherence.
Asthma step-down criteria: well-controlled for at least 3 months; no unresolved triggers; consider stepping down to the lowest effective dose that maintains control. Remove oral corticosteroids first, then reduce ICS dose; do not remove ICS entirely until the patient is at step 2 or 1 and has been stable for 6 months or more.
COPD ICS initiation criteria: blood eosinophils 300 cells per microliter or higher (strong evidence); 100–299 cells per microliter with frequent exacerbations (intermediate evidence); avoid below 100 cells per microliter. ICS withdrawal in COPD: consider if no exacerbation benefit and pneumonia has occurred, particularly with eosinophils below 100 cells per microliter.
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