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MyDeficiencies

Salmeterol

selective long-acting beta-2 adrenoceptor agonist (inhaled)

Also sold as Serevent Diskus, Seretide.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Salmeterol has almost no classical depletion machinery. Inhaled doses give very low plasma levels (mean peak 167 pg/mL), the drug is cleared by CYP3A4 hydroxylation and fecal and urinary excretion, it is not described as inducing or inhibiting any enzyme, and neither the US label nor the UK SmPC mentions any vitamin or mineral as a depletion target [1][2]. The one real nutrient-level signal is a pharmacologic one: beta-2 stimulation drives potassium into cells, and single supratherapeutic inhaled doses (100 to 400 mcg, versus the labeled 50 mcg) lowered plasma potassium in several independent healthy-volunteer studies, by 0.38 mmol/L (95% CI 0.11 to 0.65) after 300 mcg [5] and by 0.39 mmol/L (95% CI 0.28 to 0.49) after cumulative 400 mcg [4]. A cumulative-dose study in 12 asthma patients (to 375 mcg) found a similar fall, but at the labeled single dose of 50 mcg a placebo-controlled study in 12 asthma patients found no potassium fall (change +0.10 versus +0.08 mmol/L on placebo) [25][26]. This is graded orange, bounded to transient redistribution at supratherapeutic exposure. It is a shift of potassium between compartments, not a loss of body potassium, and it is not a dietary deficiency (Hard Rules 2 and 5).

selective long-acting beta-2 adrenoceptor agonist (inhaled) · ATC R03AC12 (WHO ATC/DDD Index [3]) · also sold as Serevent Diskus and Serevent Accuhaler; in Advair and Seretide and Wixela (with fluticasone) · reviewed 2026-10-08. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Salmeterol in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Potassium: transient fall in plasma potassium (shift into cells) after single supratherapeutic inhaled doses in healthy volunteers

Orange — Moderate

See study details

Direction: redistribution (intracellular shift), not depletion. Single inhaled salmeterol doses of 100 to 400 mcg lowered plasma or serum potassium by roughly 0.4 mmol/L in healthy adults for hours; this is not shown to lower total body potassium or to require dietary potassium.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. Orange

Limits on what this shows

  • Null findings: At recommended doses in label trials, "no changes in potassium were noted" in COPD trials and no clinically relevant glucose or potassium changes in pediatric laboratory data [1]. Erythromycin co-administration (13 subjects) did not change plasma potassium [1]. Salpeter's meta-analysis of beta-agonist trials (single-dose arm 13 trials, 232 patients, albuterol and salmeterol) called the potassium fall clinically unimportant, but it was not stratified by drug and was read only through a summary [10]. The HFA formulation produced a smaller fall than the CFC formulation (difference 0.12 mmol/L, below the authors' 0.3 mmol/L significance threshold) [4]. At the labeled single dose in patients, Smyth 1993 [25] found no fall at 50 mcg (+0.10 versus +0.08 on placebo, n = 12), the only placebo-controlled labeled-dose potassium result located; with 12 patients it cannot exclude a small effect.
  • At-risk subgroups: People using salmeterol with non-potassium-sparing diuretics (label warning), people in acute severe asthma, overdose, and people with diabetes for glucose [1][2]. Concomitant strong CYP3A4 inhibitors raise systemic exposure about 16-fold by AUC and are not recommended [1].

Regulatory status

US label 5.10: beta-agonists may cause significant hypokalemia, possibly through intracellular shunting; clinically significant dose-related changes in serum potassium were seen infrequently at recommended doses, and no potassium change was noted in COPD trials [1]. SmPC 4.4: "Potentially serious hypokalaemia may result from beta-2 agonist therapy"; monitor potassium in acute severe asthma; listed as rare in 4.8; overdose can cause hypokalaemia [2].

Population evidence

Kirby 1995 [4]: 12 healthy men, randomized double-blind crossover, cumulative salmeterol 400 mcg (50, 50, 100, 200 mcg at 60-minute intervals) from an HFA134a inhaler versus placebo: plasma potassium -0.39 mmol/L (95% CI -0.49 to -0.28); glucose +0.90 mmol/L (95% CI 0.58 to 1.21); QTc median difference +23 ms (95% CI 8 to 33); pulse +8 bpm (3 to 14). Grove and Lipworth 1996 [5]: 8 healthy subjects, single 300 mcg dose, serum potassium 1 hour after dosing 3.74 to 3.48 mmol/L versus placebo 3.74 to 3.84; difference from placebo -0.38 mmol/L (95% CI -0.65 to -0.11). Bennett and Tattersfield 1997 [6]: 14 healthy subjects, 100, 200, 400 mcg, plasma potassium fell dose-dependently over 4 hours with the largest individual fall -1.3 mmol/L; potency relative to salbutamol 8.2 (95% CI 5.7 to 12.6); 400 mcg glucose rise up to 2.3 mmol/L (SE 0.36). Guhan 2000 [7]: 16 healthy subjects (15 completed all visits), salmeterol 100, 200, 400 mcg versus formoterol and placebo, baseline plasma potassium about 4.0 to 4.1 mmol/L, a dose-related fall (Figure 3 axis spans about 3.3 to 4.2 mmol/L over 8 hours) that was still present at 8 hours after salmeterol but not formoterol; per-dose values are plotted in Figure 3 only and the text gives none (the fetch tool could not read the figure). Maconochie 1992 [8]: 10 healthy men, 100, 200, 400 mcg, significant dose-related changes in plasma potassium and glucose versus placebo; the abstract, a second independent record of it (OpenAlex) and the PMC landing page were opened and none gives numbers, and the full-text PDF could not be read. Maconochie 1994 [9]: 12 healthy men after 13 days of 100 mcg twice daily or placebo, cumulative doses to 400 mcg: dose-related plasma potassium changes were reported (the abstract text available did not say whether they differed by pretreatment arm); tachyphylaxis was reported for tremor, QTc and glucose. Patients, not volunteers: Bennett 1994 [26], 12 adults with mild asthma (11 on regular inhaled steroid), randomized double-blind crossover, hourly cumulative salmeterol 25, 50, 100, 200 mcg (375 mcg total) versus placebo: maximal change in plasma potassium -0.52 mmol/L (SE 0.10) on salmeterol versus -0.13 (SE 0.12) on placebo, a difference of about -0.39 mmol/L (author subtraction; the paper gives no CI or P value for the comparison), dose-dependent, median systemic dose equivalence versus salbutamol 7.8 (IQR 3.7 to 10.7). Smyth 1993 [25]: 12 adults with mild asthma (nine on regular inhaled steroid), single salmeterol 50, 100 or 200 mcg versus placebo before salbutamol, plasma potassium change from baseline mean (SE): placebo +0.08 (0.11), salmeterol 50 mcg +0.10 (0.10), 100 mcg -0.17 (0.09), 200 mcg -0.05 (0.08) mmol/L; no CI or P value for these changes is given and the response was not monotonic across doses. Kemp 1993 [27]: 24 patients with moderate asthma, single doses 12.5 to 100 mcg versus placebo; blood potassium appears in the indexing metadata but no potassium values are in the record, so it is not used.

Mechanism

Named. Beta-2 receptor stimulation increases Na/K-ATPase activity and moves potassium into skeletal muscle and other cells; the US label calls this "intracellular shunting" [1]. The effect is a redistribution of existing potassium, not a loss from the body.

Boundary

All quantified data are single or cumulative-dose studies in healthy volunteers at 2 to 8 times the labeled single dose (50 mcg), with potassium sampled for 1 to 8 hours; the asthma-patient cohort [26] reached a similar fall only at a cumulative 375 mcg. The one placebo-controlled labeled-dose result in patients (50 mcg, n = 12) showed no fall [25]. No data on persistent hypokalemia during chronic labeled-dose use were retrieved.

Related effects (not graded as nutrients)

The same studies show dose-related rises in blood glucose [4][6][8][9], heart rate and QTc [4][6][9], and tremor. These are pharmacologic effects of beta-2 agonism (Hard Rule 2) and are monitored, not filed as nutrient entries. QTc lengthening at labeled doses is small; the label ties clinically significant prolongation to doses 12 to 20 times those recommended and to strong CYP3A4 inhibitors [1]. Blood lactate is covered under the ATP entry.

Counter-evidence held on record

Counter-evidence and confounding The magnitude at the labeled dose is small to absent: no fall at 50 mcg in asthma patients [25] and infrequent clinically significant change in the label [1]. The two patient cohorts [25][26] come from the same Nottingham research unit as [6][7], so they add a population, not a fully independent group. Volunteer studies used dose escalation. After 13 days of repeated dosing, tachyphylaxis was reported for glucose, QTc and tremor, and potassium was not listed among them in the abstract text available [9]. In patients, diuretics, systemic corticosteroids and acute illness confound any observed hypokalemia. Framing caution This is a transient excess-shift (redistribution) risk, not a dietary potassium deficiency. Potassium intake should not be increased on the strength of this entry, and supplementation would be the hazard, not the remedy. Any potassium replacement after an overdose or acute severe asthma is a clinical decision for a prescriber [2].

Grapefruit and CYP3A4: food-on-drug timing interaction (direction reversed), class extrapolation

Yellow — Low

See study details

Salmeterol exposure rises sharply with strong CYP3A4 inhibitors; grapefruit is a weaker, intestinal CYP3A4 inhibitor, and no salmeterol-grapefruit study was found. This is food affecting the drug, not the drug depleting a nutrient.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: None located for salmeterol. A web search for a salmeterol grapefruit study returned the consumer interaction page and general grapefruit-interaction reviews, which were not opened. A PubMed listing for "salmeterol grapefruit" returned a 404 page (possibly zero records; not confirmed) after two earlier 429 rate-limit failures.

Regulatory status

Salmeterol is a CYP3A4 substrate; strong inhibitors are not recommended because cardiovascular adverse effects may increase [1][2]. Grapefruit is not mentioned in the label sections read.

Population evidence

Tier A for ketoconazole (salmeterol in the cohort): AUC ratio 15.76 (90% CI 10.66 to 23.31), Cmax 1.4-fold, mainly from higher bioavailability of the swallowed fraction; two of three withdrawals had prolonged QTc [1]. Erythromycin, a moderate inhibitor: Cmax 1.4-fold, AUC 1.2-fold (non-significant) in the SmPC [2]. Grapefruit was not in any cohort: CLASS EXTRAPOLATION from CYP3A4 inhibitors, salmeterol not studied with grapefruit, capped at yellow. A consumer page rates the combination "Major" by inference from other CYP3A4 substrates and a second-hand QT citation, naming no salmeterol study [23] (Tier D, not used as evidence).

Mechanism

Present: gut-wall and hepatic CYP3A4 inhibition could raise the swallowed fraction of salmeterol, which the label identifies as the main driver of the ketoconazole effect [1]. The size of any grapefruit effect on an inhaled drug is unknown.

Direction check (Hard Rule 4)

Food affects drug exposure; no nutrient is lost. Filed as a timing and exposure interaction. No separation interval is established for grapefruit with an inhaled drug.

Counter-evidence held on record

Counter-evidence and confounding Inhalation delivers most of the therapeutic dose to the lung, so the swallowed fraction is small in normal use; the ketoconazole result is for a very strong inhibitor and cannot be scaled to grapefruit. Framing caution An interaction flag for a pharmacist conversation, not a nutrient finding. It implies no supplement.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden: non-adverse direction in animal and cell data; formoterol biogenesis finding is class extrapolation

Yellow — Low

See study details

No study shows salmeterol damaging mitochondria. Animal and cell studies point toward neutral or restorative effects, and a related beta-2 agonist (formoterol) increases mitochondrial biogenesis in mice and kidney cells.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: A search for salmeterol toxicity to mitochondria in epithelial, hepatic or cardiac cells returned no salmeterol-specific adverse result. The Dowling 1997 nasal epithelium study (salmeterol reduced Pseudomonas toxin-induced cell damage; mitochondrial damage is among listed toxin effects) was seen only as a listing summary and is not relied on.

Regulatory status

No mitochondrial statement in the label sections read [1][2].

Population evidence

Tier B, salmeterol tested: Shafiek 2025 [17], 30 male Sprague-Dawley rats (10 per group), reserpine-induced fibromyalgia model: reserpine disturbed mitochondrial function and dynamics, and 21 days of intraperitoneal salmeterol reversed these effects with the pain behaviors (abstract only via a reconstructed OpenAlex record; dose and specific mitochondrial assays not available). Velez 2019 [18]: cultured gilthead sea bream muscle cells, salmeterol raised the beta-oxidation gene cpt1a and, with formoterol and noradrenaline, hadh mRNA; transcript level only, from a PubMed listing summary, not opened. No human mitochondrial data with salmeterol were found.

Class extrapolation

CLASS EXTRAPOLATION (Tier C): Wills 2012 [19] reported that formoterol increased FCCP-uncoupled oxygen consumption in renal proximal tubule cells and mtDNA copy number and PGC-1alpha in mouse kidney and heart. Salmeterol is not named in the abstract read. Peterson 2013 [20] tested a panel of beta-2 agonists in renal cells (full MB, partial MB and non-MB phenotypes not tied to receptor affinity), but the abstract and the PubMed record (PMID 23954364, opened in the repair pass, including MeSH and substance lists) name no compounds, and the full text could not be opened (PMC reCAPTCHA, ScienceDirect and the OpenAlex content copy refused), so whether salmeterol was in that cohort is unknown. Cohort test: salmeterol was not confirmed in the formoterol cohort; capped at yellow and not used to claim a salmeterol effect.

Mechanism

Plausible but unestablished for salmeterol: beta-2 signaling to PGC-1alpha-linked biogenesis is documented for formoterol; the structural differences of salmeterol (long lipophilic side chain, partial agonism) mean it cannot be assumed.

Counter-evidence held on record

Counter-evidence and confounding The rat model used a mitochondrial-injuring toxin and the effect may be secondary to improved pain signaling; the fish cell work is transcript-only in a different species. Neither translates to human mitochondrial output. Framing caution Not a finding of mitochondrial damage or benefit. Do not extend formoterol biogenesis data to salmeterol.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress: reverse direction, suppression of superoxide release from activated leukocytes in vitro

Yellow — Low

See study details

Salmeterol reduced reactive-oxygen output from stimulated human neutrophils and eosinophils in vitro, a protective rather than depleting chemistry; the only human marker data are confounded by fluticasone co-treatment.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: A trial in 36 asthma patients comparing fluticasone alone with fluticasone plus salmeterol found "similar changes" in neutrophil lipid peroxidation and antioxidant enzymes in both arms (English abstract of a Russian paper; no numbers) [16], so adding salmeterol did not measurably change the redox picture beyond fluticasone. Well-controlled asthma patients on inhaled steroid plus long-acting beta-2 agonist still had higher serum lipid peroxides than healthy controls (PMID 17539852, listing record only; not opened, not cited as evidence).
  • At-risk subgroups: None identified; no adverse redox signal exists for salmeterol.

Regulatory status

No oxidative-stress or antioxidant statement in the US label or SmPC sections read [1][2].

Population evidence

In vitro (Tier B): Ottonello 1996 [13], human neutrophils on fibronectin stimulated with fMLP, salmeterol inhibited the superoxide burst dose-dependently while salbutamol had no effect; propranolol did not reverse it and it did not track cAMP (abstract only; concentrations and percentages were not available in the record). Ezeamuzie 1998 [14], purified human eosinophils, IL-5-induced superoxide release inhibited with IC50 2.2 x 10^-6 M (95% CI 1.6 to 2.7 x 10^-6 M) and maximum inhibition about 70%; salbutamol had no effect at 10^-5 M; salmeterol's action was independent of beta-2 receptors. Human, confounded (Tier A for the combination, not for salmeterol alone): Ozaras 2000 [15], 14 non-smoking mild-to-moderate asthma patients given salmeterol 100 mcg/day plus fluticasone propionate 500 mcg/day for one month: serum malondialdehyde 6.7 +/- 0.8 to 5.3 +/- 0.7 nmol/mL (P < 0.001) versus 3.8 +/- 0.4 in 24 healthy controls (still higher, P < 0.0001), alongside FEV1 2.43 to 3.50 L, with no salmeterol-free arm.

Mechanism

Present, partly receptor-independent: both leukocyte studies found the effect did not follow classic beta-2 receptor or cAMP signaling [13][14]. The authors of [13] link the effect to salmeterol's receptor-binding behavior (wording ambiguous in the abstract).

Counter-evidence held on record

Counter-evidence and confounding The malondialdehyde fall [15] is confounded by fluticasone and by improved disease control (FEV1 rose 1.07 L); it says nothing about salmeterol alone. In vitro concentrations are micromolar, far above the plasma levels from inhaled dosing (about 200 pg/mL or less [2], roughly 0.5 nanomolar by calculation). Framing caution This is a reverse-direction mechanism note, not evidence of an antioxidant benefit or of antioxidant depletion. No antioxidant supplement is implied.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper

Not graded — disclosed evidence gap

See study details

No evidence was found that salmeterol changes copper status, binds copper, or is claimed to do so.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source supports even yellow, and no circulating claim of salmeterol copper depletion or excess was found to rebut. A disclosed gap, not a finding of safety. Kept separate from iron (Hard Rule 7).

What was searched

PubMed listing "salmeterol copper" (3 records: a copper-catalyzed synthesis of a salmeterol intermediate, a copper disc used as a force target in an inhaler plume study, and an index-term mention in a rat airway leak study; none measures copper status). The US label and SmPC contain no copper statement [1][2]. Nutrient-depletion chart from Natural Medicines [24] lists no beta-2 agonist entry. The listing was screened for xinafoate (hydroxynaphthoic acid) chelation work and none was flagged. Repair pass: PubMed listing "salmeterol ceruloplasmin" returned 0 records (opened, 2026-10-08).

Channel outcomes

PubMed listing: opened after two 429 rate-limit retries. WebSearch for copper-specific queries: not run because the shared web search budget was exhausted. PMC and Europe PMC: bot-verification or blocked. Repair pass: WebSearch was attempted and refused because the shared search budget was used up; the ceruloplasmin listing opened with zero records; a combined OR query returned the PubMed home page (no results parsed) and was not repeated after a 429. This is a genuine gap on the PubMed channel, with limited tooling breadth (no web search, no Europe PMC).

Iron

Not graded — disclosed evidence gap

See study details

No evidence was found that salmeterol changes iron absorption, ferritin, serum iron or hemoglobin, and no consumer claim exists.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source and no circulating claim. A disclosed gap, not a finding of safety. Kept separate from copper and from the oxygen delivery entry (Hard Rule 7).

What was searched

PubMed listing "salmeterol AND (iron OR ferritin OR hemoglobin OR anemia OR methemoglobin)": 7 records, none measuring an iron or hematologic analyte with salmeterol (an oxygen-saturation study in cystic fibrosis [21], a levofloxacin hepatitis case in a salmeterol-fluticasone user without hemoglobin values, and unrelated reviews). Label sections read contain no iron statement [1][2]; the Natural Medicines chart lists none [24]. Repair pass: PubMed listings "salmeterol serum iron ferritin" and "salmeterol methemoglobin" each returned 0 records (opened, 2026-10-08).

Channel outcomes

PubMed listing: opened. Web search for iron-specific phrasings: not run in the original review (budget exhausted) and refused again in the repair pass (budget exhausted). Genuine gap on the PubMed channel; no inhaled-drug iron-interaction mechanism is plausible from the pharmacokinetics (negligible systemic exposure, no gastrointestinal action).

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk

Not graded — disclosed evidence gap

See study details

No study of salmeterol exposure with gut or fecal microbiota composition was found, and no circulating microbiome claim for this drug.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Dual condition met: no Tier B or C source with salmeterol as the exposure, and no circulating claim. The fluticasone component of combination inhalers is not attributed to salmeterol. A disclosed gap, not a finding of safety.

What was searched

PubMed listings "salmeterol gut microbiome" (1 record, a drug-repurposing target-trial emulation in which salmeterol was one exposure and no microbiota was measured) and "salmeterol OR fluticasone AND (fecal microbiota OR gut dysbiosis OR intestinal microbiota)" (4 records: two fluticasone mouse studies with cecal microbiome change, one pesticide study, and the same repurposing study). Fluticasone mouse data (Asai 2023, Yagi 2024) were seen as listing summaries only and are excluded: they concern a different drug and were not opened. Repair pass: "salmeterol difficile" returned 0 records; "salmeterol dysbiosis OR fecal microbiota OR 16S" returned 4 records, all airway or pulmonary microbiome work. The one with a salmeterol arm that was opened, the DISARM randomized trial in 63 COPD patients [28] (fluticasone/salmeterol 250/50 mcg twice daily, n = 22, versus budesonide/formoterol and formoterol alone, 12 weeks, 16S rRNA, bronchoscopy), found lower airway alpha-diversity with the fluticasone/salmeterol combination than with formoterol (delta richness P = 0.02, delta Shannon P = 0.03) and attributes the shift to the fluticasone-based ICS. That is airway, not gut, and the combination cannot isolate salmeterol, so it does not grade this gut entry. Two further airway records (PMID 35625847, 40841147) were listing summaries only and not opened.

Channel outcomes

PubMed listings opened; Europe PMC REST: 429; web search budget exhausted before microbiome phrasings could be tried and refused again in the repair pass. 16S, dysbiosis, fecal microbiota and C. difficile phrasings were run on PubMed in the repair pass (results above); a "salmeterol gut microbiota" listing hit a 429 and was not repeated. Gut-site evidence is a genuine gap on the PubMed channel; web search and Europe PMC breadth remain tooling-limited.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

ATP production: indirect lactate signal only at overdose; no ATP or respiration measurement

Yellow — Low

See study details

Beta-2 agonists stimulate glycolysis and can raise blood lactate; for salmeterol this is documented only as a lactic acidosis case after a 60-puff overdose, and nothing measured cellular ATP.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: No study measuring ATP content, oxygen consumption or mitochondrial membrane potential with salmeterol was found (PubMed listing "salmeterol mitochondrial" returned no such endpoint in a human or cell-respiration study).

Regulatory status

Lactate is not mentioned in the visible US label content [1]; the SmPC overdose section mentions hypokalaemia [2].

Population evidence

Tier B: Manara 2012 [11], one 16-year-old who inhaled 60 puffs of salmeterol 25 mcg plus fluticasone 50 mcg and presented about 2 hours later with lactic acidosis and hypokalemia (values not given in the abstract), sinus tachycardia and ST depression, normal troponin; findings resolved with supportive care and cautious potassium the next day. Tier C: Liedtke 2020 [12], systematic review of 56 reports on selective beta-2 agonist hyperlactatemia, dominated by albuterol (mostly nebulized); salmeterol appears only as a literature-search term in its methods, and one case involved an unnamed long-acting beta-2 agonist, so salmeterol is not confirmed in the cohort and this is class extrapolation. Healthy-volunteer lactate rises there were with albuterol (about 0.8 mmol/L nebulized, about 2.0 mmol/L intravenous).

Mechanism

Present as a metabolic-demand effect (class I): beta-2 stimulation increases glycogenolysis and glycolytic flux, producing lactate with intact mitochondria. This is not evidence of impaired oxidative phosphorylation.

Counter-evidence held on record

Counter-evidence and confounding The overdose case is a single patient with combination product exposure, and lactic acidosis in asthma has other drivers (work of breathing, hypoxia). Hyperlactatemia is a drug effect, not an ATP deficit (Hard Rule 2). Framing caution Not a claim of reduced energy production. No fatigue or "low energy" inference should be drawn from this entry.

Oxygen delivery/utilization: mechanism clarification, arterial saturation improves through bronchodilation; no hemoglobin or iron data

Yellow — Low

See study details

The only salmeterol oxygen-related human trial found showed higher overnight oxygen saturation, which is the drug's intended airway effect; nothing was found on hemoglobin, red-cell mass or methemoglobin.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

  • Null findings: No hematologic adverse signal for salmeterol was found. A case of worsening anemia in a patient on salmeterol-fluticasone was concomitant to levofloxacin hepatitis and had no hemoglobin values (PMID 21194596, listing only; not opened, not used).

Regulatory status

No hemoglobin, hematocrit or oxygen-carrying statement in the label sections read [1][2].

Population evidence

Salvatore 2002 [21]: 23 patients with cystic fibrosis and sleep desaturation, double-blind crossover, salmeterol versus placebo before sleep: mean overnight transcutaneous saturation and FEV1 and FEF25-75 improved, but only in albuterol responders (dose and numbers not available; reconstructed OpenAlex abstract). A PubMed listing for salmeterol with iron, ferritin, hemoglobin, anemia and methemoglobin terms found no study measuring those analytes.

Mechanism

Clarification: improved ventilation through bronchodilation raises arterial saturation. This is the intended pharmacologic effect and a clinical outcome, so it is not filed as a delivery finding or a nutrient deficiency (Hard Rule 2). Transient ventilation-perfusion effects of beta-agonists on arterial oxygen tension were not retrieved for salmeterol.

Counter-evidence held on record

Counter-evidence and confounding Selected cystic fibrosis responders are not a general population; there is no evidence of a drug effect on oxygen-carrying capacity either way. Framing caution Not an oxygen-delivery deficiency and not a benefit claim. Kept separate from the ATP and iron entries (Hard Rule 7).

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Magnesium "depleted" (white)

    Where it comes from: Consumer drug-information page (University of Michigan Health library; a PeaceHealth page with the same ID appeared in search results and was not opened) listing potassium, calcium and magnesium under "Replenish Depleted Nutrients" for salmeterol, citing a study of four healthy people given intravenous albuterol [22].

    Why it fails: The page's source is albuterol, not salmeterol, and it states that whether the changes are preventable by diet or supplements is unknown. For salmeterol, plasma magnesium was measured in 12 healthy men after cumulative doses to 400 mcg and showed no dose-related effect [9] (abstract only; no values; small sample and circulating, not total-body, magnesium). The label content read contains no magnesium statement [1][2].

  • Calcium and phosphate (provisional, tooling-limited)

    Where it comes from: Same consumer page [22].

    Why it fails: No salmeterol measurement of calcium or phosphate was found, and the intravenous albuterol source the page relies on was not opened. A plausible beta-agonist class effect is not excluded, so this is not graded white on the merits. Held out as a deficiency claim pending a re-check that could convert it to yellow.

  • Potassium "depletion" needing replenishment

    Where it comes from: Same consumer page [22].

    Why it fails: Not white: the potassium fall is real but transient and a redistribution into cells, observed at supratherapeutic single doses [4][5], and is graded orange with that boundary. The "depleted nutrient to replenish" framing is not supported; the page itself rates the evidence preliminary and contradictory.

  • Grapefruit additive QT prolongation with salmeterol (white as stated)

    Where it comes from: Consumer interaction page rating grapefruit with salmeterol "Major" on QT and CYP3A4 grounds [23].

    Why it fails: The QT claim cites a grapefruit-juice QT study in volunteers drinking 6 liters over 6 hours (second-hand, not opened) and no salmeterol study; the page's own commentary says a normal serving is unlikely to matter, and its evidence grade is internally inconsistent. The CYP3A4 part is carried as a yellow class-extrapolation entry.

How the body handles this medication

Metabolism and enzymes
Extensively metabolized by hydroxylation; CYP3A4 forms alpha-hydroxysalmeterol, and ketoconazole essentially completely inhibited this in vitro. Salmeterol is a CYP3A4 substrate. No CYP induction or inhibition by salmeterol is described in the label sections read.[1] DailyMed Serevent Diskus label, sec 7.1, 12.3 (read via summarizing fetch tool)
Elimination
After 1 mg oral radiolabeled salmeterol in 2 subjects, about 25% appeared in urine and 60% in feces over 7 days. Terminal half-life about 5.5 hours (one volunteer). The xinafoate counter-ion has a half-life of about 11 days and is more than 99% protein bound.[1] sec 12.3
Absorption and plasma level
Plasma levels after inhalation are very low: mean peak 167 pg/mL at 20 minutes, with no accumulation on repeat dosing. The UK SmPC gives about 200 pg/mL or less and states that salmeterol acts locally, so plasma levels do not predict effect. Plasma protein binding averages 96% in vitro. No named absorption transporter is given.[1] sec 12.3; [2] sec 5.2
CYP3A4 inhibitor interaction
Ketoconazole 400 mg daily with salmeterol 50 mcg twice daily for 7 days: AUC ratio 15.76 (90% CI 10.66 to 23.31), Cmax up 1.4-fold (90% CI 1.23 to 1.68), mainly from increased bioavailability of the swallowed fraction. The US label reports 20 healthy subjects, three of whom withdrew, two with prolonged QTc; the SmPC reports 15 subjects (the two documents differ on this count). Erythromycin (13 subjects): QTc up 5.8 ms (95% CI -6.14 to 17.77, P = 0.34), no change in plasma potassium. Strong CYP3A4 inhibitors are not recommended.[1] sec 7.1, 12.3; [2] sec 4.5
Label statements on electrolytes and glucose
Section 5.10: beta-agonists may cause significant hypokalemia, possibly through intracellular shunting; clinically significant dose-related changes in glucose or potassium were seen infrequently at recommended doses. Section 5.6: QTc prolongation has been associated with doses 12 to 20 times the recommended dose. Non-potassium-sparing diuretics may worsen ECG changes or hypokalemia. The SmPC lists hypokalemia as rare and hyperglycemia as very rare.[1] sec 5.6, 5.10, 7; [2] sec 4.4, 4.8
Nutrient, food and renal handling
The label content read contains no vitamin, mineral or dietary nutrient statement and no renal tubular effect. The only food-related text is the lactose excipient, which contains milk proteins (severe milk protein allergy warning). Part of the US label (after section 14.1) was not read because the fetch tool truncated the page.[1] sec 5.7, 11
Mechanism screen (classes A to I)
Absent: A absorption interference, B enzyme induction, C renal wasting, D cofactor antagonism, E mitochondrial conjugation loss, G microbiome disruption, H changed intake. Present: F hormonal/transport disturbance (beta-2 stimulation of Na/K-ATPase uptake, shifting potassium into cells) and I increased metabolic demand (glycolysis and lactate). Carried forward: potassium, and by extension glucose, lactate and magnesium as screened items.Author synthesis of [1][2][4][5]

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

  • Lab / specific situations

    Serum potassium

    Worth checking in acute severe asthma, after an overdose, or when salmeterol is used with non-potassium-sparing diuretics, as the labels advise [1][2]. At routine labeled doses a transient fall is small and infrequently significant. This is a monitoring prompt for a transient shift, not a prompt to increase potassium intake.

  • Lab / diabetes

    Blood glucose

    Dose-related glucose rises occurred in volunteer studies at supratherapeutic doses [4][6]. The SmPC advises caution in people with diabetes [2].

  • ECG / interactions

    QTc and CYP3A4 inhibitors

    Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, telithromycin) raise salmeterol exposure about 16-fold by AUC and are not recommended [1][2]. MAO inhibitors and tricyclic antidepressants need extreme caution per the label [1]. Large regular grapefruit intake is a question for a pharmacist.

  • Re-check list

    Entries to re-run when access improves

    Copper, iron and gut microbiome (16S, dysbiosis, C. difficile phrasings); calcium and phosphate (open the intravenous albuterol source); the Peterson 2013 mitochondrial panel full text for salmeterol (still unreadable after the repair pass); Maconochie 1992 and Guhan 2000 Figure 3 per-dose potassium values (still not recoverable); a second placebo-controlled potassium study at 50 mcg.

  • Timing

    Supplement separation

    No mineral or vitamin separation interval is listed in the label sections read. No supplement dose is recommended or appears anywhere in this dossier, so no upper-limit comparison was needed.

  • Special populations

    Pregnancy, pediatrics, milk allergy

    Pregnancy and pediatric nutrient considerations were not assessed from the label sections read. The lactose excipient contains milk proteins and the label warns against use in severe milk protein allergy [1].

Overlap map, to prevent double counting

  • Potassium (orange)

    Shares evidence with: Fails verification: magnesium; the non-nutrient glucose and QTc effects

    Note: The volunteer studies [4][6][8][9] report potassium, glucose, QTc and pulse together; the Maconochie 1994 study [9] is also the source of the magnesium null. Studies [6] and [7] share authors (Bennett JA, Tattersfield AE) and use similar healthy-volunteer dose-escalation designs, so they are not fully independent confirmations of one another's methods. The asthma-patient studies [25][26] are from the same Nottingham unit and report potassium alongside heart rate and QTc; [25] also supplies the labeled-dose null. Kemp 1993 [27] is used nowhere for numbers. Glucose and QTc are not counted as separate entries.

  • ATP production

    Shares evidence with: Potassium (the overdose case)

    Note: The Manara case [11] reports lactic acidosis and hypokalemia together; the hypokalemia is part of the potassium mechanism and lactate is the only ATP-entry content. One case, not two lines of evidence.

  • Mitochondrial burden

    Shares evidence with: ATP production; Oxidative stress

    Note: No shared source. The rat fibromyalgia study [17] is cited only for mitochondria; leukocyte superoxide data [13][14] only for oxidative stress. Both ATP and mitochondrial entries rest on the same absence of respiration or ATP assays with salmeterol, a single gap viewed twice.

  • Oxidative stress

    Shares evidence with: none beyond the common beta-2 signaling mechanism

    Note: The malondialdehyde study [15] is a salmeterol plus fluticasone combination and is used only here.

  • Oxygen delivery/utilization

    Shares evidence with: Iron (ungraded)

    Note: Any hemoglobin-mediated effect would run through iron; neither has data. The cystic fibrosis saturation study [21] is used only in the oxygen entry and is listed as context in the iron channel summary.

  • Copper

    Shares evidence with: Iron

    Note: No shared source; both ungraded from separate listings. Graded separately per Hard Rule 7.

  • Grapefruit and CYP3A4

    Shares evidence with: Potassium; QTc effect

    Note: The label's ketoconazole and erythromycin studies [1] are also the source of the QTc and potassium observations in the PK basis. Shared label source, not independent confirmation.

All references used above
  1. SEREVENT DISKUS (salmeterol xinafoate) inhalation powder, prescribing information, GlaxoSmithKline LLC (DailyMed). — Regulatory label (Tier A). Revised 10/2022. Sections 5.6, 5.7, 5.10, 6, 7.1, 11, 12.2, 12.3 read. Read through a summarizing fetch tool; the page was truncated and the final 9,185 characters (after section 14.1) were not read.
  2. Serevent Accuhaler, Summary of Product Characteristics (electronic medicines compendium, UK). — Regulatory label (Tier A). Updated 8 Sep 2023 (section 10 date 31/08/2023). Sections 4.4, 4.5, 4.8, 4.9, 5.2 read through a summarizing fetch tool.
  3. WHO Collaborating Centre, ATC/DDD Index: salmeterol, R03AC12, DDD 0.1 mg inhalation. — Reference index; parent group R03AC selective beta-2-adrenoreceptor agonists.
  4. Kirby SM, Smith J, Ventresca GP. Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic pharmacodynamic activity in healthy volunteers. Thorax 1995;50(6):679-681. — Randomized double-blind three-way crossover, 12 healthy men, cumulative salmeterol 50 to 400 mcg versus placebo. Tier A. Full-text PDF table read via a summarizing fetch tool; the pulse-rate slope text was garbled in extraction and the QTc row is medians.
  5. Grove A, Lipworth BJ. Evaluation of the beta-2 adrenoceptor agonist/antagonist activity of formoterol and salmeterol. Thorax 1996;51:54-58. — Randomized single-dose study, 8 healthy volunteers, salmeterol 300 mcg, formoterol 72 mcg, propranolol 80 mg versus placebo. Tier A. Full-text PDF table read via a summarizing fetch tool.
  6. Bennett JA, Tattersfield AE. Time course and relative dose potency of systemic effects from salmeterol and salbutamol in healthy subjects. Thorax 1997;52:458-464. — Double-blind randomized crossover, 14 healthy subjects, salmeterol 100, 200, 400 mcg and salbutamol 600 to 2400 mcg MDI. Tier A. Full-text PDF read via a summarizing fetch tool; per-dose means are in figures and were not retrieved.
  7. Guhan AR, Cooper S, Oborne J, Lewis S, Bennett J, Tattersfield AE. Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects. Thorax 2000;55:650-656. — Double-blind randomized crossover, 16 healthy subjects, salmeterol 100, 200, 400 mcg Diskhaler versus formoterol and placebo, 8-hour monitoring. Tier A. Full-text PDF read via a summarizing fetch tool twice (original review and repair pass); baseline potassium (Table 1) and the formoterol:salmeterol potency ratio (Table 2: 5.8, 95% CI 4.1 to 8.6 over 4 hours; 3.0, 1.2 to 5.7 over 8 hours) were read, but the per-dose potassium values are in Figure 3 and were not recoverable.
  8. Maconochie JG, Forster JK. Dose-response study with high-dose inhaled salmeterol in healthy subjects. Br J Clin Pharmacol 1992;33(3):342-345. — Double-blind placebo-controlled crossover, 10 healthy men, salmeterol 100, 200, 400 mcg and salbutamol 400 mcg. PMID 1349491; DOI 10.1111/j.1365-2125.1992.tb04049.x. Tier A. Abstract only (BPS page and a reconstructed OpenAlex record, re-opened in the repair pass, and the PMC landing page PMC1381289, which carries the abstract only); no numerical results; the Wiley PDF and PMC PDF could not be read.
  9. Maconochie JG, Minton NA, Chilton JE, Keene ON. Does tachyphylaxis occur to the non-pulmonary effects of salmeterol? Br J Clin Pharmacol 1994;37(2):199-204. — Double-blind two-period crossover, 12 healthy men, 100 mcg twice daily or placebo for 13 days then cumulative doses to 400 mcg. PMID 7910472; DOI 10.1111/j.1365-2125.1994.tb04261.x. Tier A. Abstract only via a reconstructed OpenAlex record (truncated near 250 words).
  10. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest 2004;125(6):2309-2321. — PMID 15189956. Not opened: the OpenAlex record had no abstract. Details come from an American Family Physician summary, which reports that the trials were primarily albuterol and salmeterol and not stratified by drug.Not stratified to salmeterol; context only, Tier C for this drug.
  11. Manara A, Hantson P, Vanpee D, Thys F. Lactic acidosis following intentional overdose by inhalation of salmeterol and fluticasone. CJEM 2012;14(6):378-381. — Case report, one 16-year-old, 60 puffs of salmeterol 25 mcg/fluticasone 50 mcg. Tier B. Abstract page only; no numeric values.
  12. Liedtke AG, Lava SAG, Milani GP, Agostoni C, Gilardi V, Bianchetti MG, Treglia G, Fare PB. Selective beta-2-adrenoceptor agonists and relevant hyperlactatemia: systematic review and meta-analysis. J Clin Med 2020;9(1):71. — 56 articles (42 case reports, 2 observational studies, 12 trials). Abstract and full text read via a summarizing fetch tool; salmeterol appears only as a search term, and one of 47 cases involved an unnamed long-acting beta-2 agonist (Table 1 not visible).Dominated by albuterol; salmeterol not confirmed in the cohort. Tier C for this drug.
  13. Ottonello L, Morone P, Dapino P, Dallegri F. Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils. Clin Exp Immunol 1996;106:97-102. — In vitro, human neutrophils. DOI 10.1046/j.1365-2249.1996.d01-804.x. Tier B. Reconstructed OpenAlex abstract only.
  14. Salmeterol versus salbutamol on human eosinophil function (superoxide release, adhesion, degranulation). J Pharmacol Exp Ther 1998;284(1):25. Corresponding author C. I. Ezeamuzie, Kuwait University. — In vitro, purified human eosinophils. Tier B. Page text read via a summarizing fetch tool; the full title and author list were not captured and the year is inferred from the received and accepted dates (1997) and volume 284.
  15. Ozaras R, et al. Changes in malondialdehyde levels in bronchoalveolar fluid and serum by the treatment of asthma with inhaled steroid and beta2-agonist. Respirology 2000. — Before-after study, 14 asthma patients and 24 controls, salmeterol 100 mcg/day plus fluticasone 500 mcg/day for one month. PMID 11022993. Abstract via PubMed record. Tier A for the combination; salmeterol cannot be isolated.
  16. Medvedeva IV, et al. Clinical and biochemical aspects of flixotide administration in patients with moderate bronchial asthma. Ter Arkh 2002. — Comparative trial, 36 asthma patients (18 per arm), fluticasone alone versus fluticasone plus salmeterol, 8 weeks. PMID 11980114. English abstract of a Russian paper; no numeric values.
  17. Shafiek MZ, Zaki HF, Mohamed AF. New ways to repurpose salmeterol in an animal model of fibromyalgia. Fundam Clin Pharmacol 2025;39(1):e13041 (online 2024). — Rat study, 30 male Sprague-Dawley rats. PMID 39496328; DOI 10.1111/fcp.13041. Tier B. Reconstructed OpenAlex abstract only.
  18. Velez EJ, et al. Effects of beta-2 adrenoceptor agonists on gilthead sea bream (Sparus aurata) cultured muscle cells. Comp Biochem Physiol A 2019. PMID 30347245. — In vitro, fish primary myocytes. Tier B (non-mammalian). Seen only as a PubMed listing summary; not opened.
  19. Wills LP, Trager RE, Beeson GC, Lindsey CC, Peterson YK, Beeson CC, Schnellmann RG. The beta-2 adrenoceptor agonist formoterol stimulates mitochondrial biogenesis. J Pharmacol Exp Ther 2012;342(1):106-118. — Cells and mice. Abstract via institutional repository page.Formoterol study; salmeterol not named in the abstract read. Tier C for this drug.
  20. Peterson YK, Cameron RB, Wills LP, Trager RE, Lindsey CC, Beeson CC, Schnellmann RG. Beta-2-adrenoceptor agonists in the regulation of mitochondrial biogenesis. Bioorg Med Chem Lett 2013;23(19):5376-5381. — Panel of beta-2 agonists in renal cells. Abstract via institutional repository page; PubMed record PMID 23954364 (DOI 10.1016/j.bmcl.2013.07.052) also opened in the repair pass.Compounds not named in the abstract; full text on PMC returned bot-verification. Whether salmeterol was tested is unknown. Not used for any claim.
  21. Salvatore D, D'Andria M. Effects of salmeterol on arterial oxyhemoglobin saturations in patients with cystic fibrosis. Pediatr Pulmonol 2002;34(1):11-15. — Double-blind crossover, 23 patients. PMID 12112791; DOI 10.1002/ppul.10117. Tier A for saturation. Reconstructed OpenAlex abstract only; dose and numbers unavailable.
  22. University of Michigan Health / PeaceHealth health library: salmeterol drug information page (hn-1487005). — Tier D consumer content. Used only as the origin of the potassium, calcium and magnesium "depletion" claim; it attributes the data to intravenous albuterol.
  23. HelloPharmacist. Grapefruit and Serevent (salmeterol) interaction page. — Tier D consumer content, commercial. Used only as the origin of the grapefruit "Major" interaction claim.
  24. Natural Medicines. Chart of drug-induced nutrient depletions. — Tier D reference chart. Opened to check for a salmeterol or beta-2 agonist entry: none found.
  25. Smyth ET, Pavord ID, Wong CS, Wisniewski AF, Williams J, Tattersfield AE. Interaction and dose equivalence of salbutamol and salmeterol in patients with asthma. BMJ 1993;306(6877):543-545. — Randomized double-blind crossover, 12 adults with mild asthma (nine on regular inhaled steroid), placebo or salmeterol 50, 100, 200 mcg, then cumulative salbutamol. PMID 8096416; DOI 10.1136/bmj.306.6877.543. Tier A. Full-text PDF Table I read via a summarizing fetch tool (baseline mean SD and change mean SE for plasma potassium; the text gives no CI or P value for them).
  26. Bennett JA, Smyth ET, Pavord ID, Wilding PJ, Tattersfield AE. Systemic effects of salbutamol and salmeterol in patients with asthma. Thorax 1994;49(8):771-774. — Randomized double-blind crossover, 12 adults with mild asthma (11 on regular inhaled steroid), cumulative salmeterol 25 to 200 mcg versus salbutamol and placebo, hourly doses. PMID 8091321; DOI 10.1136/thx.49.8.771. Tier A. Full-text PDF tables read via a summarizing fetch tool (OCR garbled in places); per-dose potassium values are not reported.
  27. Kemp JP, Bierman CW, Cocchetto DM. Dose-response study of inhaled salmeterol in asthmatic patients with 24-hour spirometry and Holter monitoring. Ann Allergy 1993;70(4):316-322. — Double-blind 6-way crossover, 24 patients with moderate asthma, salmeterol 12.5 to 100 mcg. PMID 8466097. Tier A for the cohort. Reconstructed OpenAlex record only (closed access); blood potassium appears in the indexing metadata but no potassium values were available, so the source is not used as evidence for any number.
  28. Leitao Filho FS, Takiguchi H, Akata K, et al. Effects of inhaled corticosteroid/long-acting beta-2-agonist combination on the airway microbiome of patients with COPD: a randomized controlled clinical trial (DISARM). Am J Respir Crit Care Med 2021;204(10):1143-1152. — Randomized trial, 63 COPD patients, fluticasone/salmeterol 250/50 mcg twice daily (n = 22) versus budesonide/formoterol and formoterol alone, 12 weeks, 16S rRNA, bronchoscopy. PMID 34464242; DOI 10.1164/rccm.202102-0289OC. Abstract via PubMed record (opened in the repair pass). Airway microbiome, not gut; the salmeterol arm is a fluticasone combination. Cited only as a non-gut finding.Airway site, combination product; does not grade the gut microbiome entry.