ASTHMA-MAINTENANCE MEDICATIONS


Inhaled Corticosteroids
Systemic Corticosteroids

Mast Cell Stabilizers

Leukotriene Modifiers

Long-Acting Beta-Adrenergic Agonists

Theophylline

Omalizumab

Others

 

  1. Inhaled Corticosteroids
  1. Reduce symptoms and objective indices of airways obstruction, prevent exacerbations/may prevent irreversible airways injury
  1. Use in COPD other than asthma--limited benefit
    1. 281 pts with COPD (all current or former smokers and with chronic productive cough) randomized to fluticasone proprionate 500mg BID vs. placebo & followed for 6mos; fluticasone group had sig. fewer exacerbations of mod. or severe intensity, sig. greater improvement in sx, exercise tolerance, and FEV1 and FVC; no sig. diff. in adverse effects between fluticasone & placebo groups (Lancet 351:773, 1998--AFP)
    2. 203 pts 30-70yo with non-asthma COPD, FEV1/VC < 0.7, and FEV1 < 15% reversible w/inhaled bronchodilators randomized to inhaled budesonide vs. placebo found no sig. diff. in FEV1, self-reported sx, or # of exacerbations over 3y of f/u (Lancet 353:1819, 1999--JW)
    3. 1277 smokers 30-65yo with mild COPD and minimal response to bronchodilators randomized to inhaled budesonide 400ug BID vs. placebo. Over the 1st 6mos, the budesonide had better maintenance of FEV1 but at 3y the FEV1 of both groups had declined to a similar degree (NEJM 340:1948, 1999--JW)
    4. 751 adults with mod-to-severe COPD randomized to inhaled fluticasone 500ug BID vs. placebo; over 3y f/u, no diff. in rate of decline of FEV1; however, sig. fewer exacerbations in fluticasone group (mean 0.99/yr vs. 1.32/yr w/placebo) (BMJ 320:1297, 2000--JW)
    5. 1116 pts with COPD randomized to triamcinolone 600ug inhaled BID vs. placebo; over avg. 40mo f/u, no diff. in mean decline in FEV1 and only slight difference in sx; nonsig. fewer hosp's in triamcinolone group (NEJM 343:1902, 2000--JW)
    6. In a systematic review of 18 studies comparing monotherapy with long-acting beta-agonists to combined therapy wish cuh agents + an inhaled corticosteroid, combined therapy was associated with sig. better FEV1 and reduced incidence of moderate COPD exacerbations but no sig. diff. in incidence of severe COPD exacerbations or mortality; furthermore, combination therapy was associated with sig. higher incidence of pneumonia (RR 1.63) (Chest 136:1029, 2009-AFP)
    7. See data on combination therapy inhaled steroids-salmeterol
  1. Adverse effects
    1. Cough
    2. Dysphonia
    3. Oral thrush
    4. Risk of ophthalmic complications
  1. Case-control study of 9793 pts > 66yo with ocular hypertension or open-angle glaucoma vs. 38,000 controls who saw ophthalmologist for other reasons. Current users of high-dose (equivalent to > 1.6mg of beclomethasone or 1.5mg of flunisolide/day) but not low dose inhaled steroids for > 3 mos had RR of 1.44 for these conditions. (JAMA 277:722, 1997-JW)
  2. Cross-sectional study of 3,000 adults age 49-97 (10% were using inhaled corticosteroids) showed that used of inhaled steroids ass'd with sig. incr. risk for both nuclear (1.5) and subcapsular (1.9) cataracts; risk increased with duration of use. Association persisted after adjustment for use of systemic steroids (NEJM 337:8, 1997-JW)
  1. May slow growth in children, though possibly with little effect on final adult height
  1. NEJM 337:1659, 1997; cited in Med. Lett.
  2. In a crossover trial comparing of inhaled budesonide 800ug QD vs. 400ug BID in 24 children (mean age 9.2y) with mild asthma (8wk total trial duration), lower-leg growth and collagen turnover were sig. slower in the BID group (J. Peds. 133:608, 1998--JW)
  3. 157 children tx'd with inhaled Budesonide (avg. 504ug/d) for avg. 4.5y compared with 111 kids with asthma not on inhaled steroids (matched for age, sex, height & weight)--no sig. diff. in bone mineral density assessed by DEXA, bone mineral capacity, or bone calcium (Am. J. Resp. Crit. Care Med. 157:178, 1998--AFP)
  4. In a randomized trial of 1041 kids 5-12yo with mild-mod asthma randomized to budesonide 200ug BID, nedocromil 8mg BID, or placebo, over 4-6y f/u, mean increase in height was slightly less in budesonide group (22.7vs c/w 23.8 for both placebo & nedocromil groups (NEJM 343:1054, 2000--JW)
  1. May adversely affect bone mineral density
    1. In a cohort study of 196 pts 20-40yo with asthma on inhaled steroids for median 6y, the cumulative inhaled corticosteroid use was inversely ass'd with BMD at the lumbar spine and femoral neck and trochanter, after adjustment for age and sex (Lancet 355:1399, 2000--JW)
    2. In a randomized trial of inhaled fluticasone 88-440ug BID vs. placebo in 160 adults with asthma, change in lumbar and proximal femoral BMD at 2y was not sig. diff. between the groups (Am. J. Resp. Crit. Care Med. 169:855, 2004--JW)
    3. In a prospective study in 1,671 pts with asthma or COPD > 75yo, over 4.7y f/u, after adjustment for potential confounders, use of inhaled steroids were associated with a dose-related increase in fracture risk (RR 4 if daily average dose > 600 ug; no sig. increase in risk if daily dose < 400 ug) (Chest 130:1082, 2006--JW)
    4. In a substudy of the "TORCH" trial, where pts with moderate-to-severe COPD were randomized to receive inhaled fluticasone vs. placebo, at 3y there was no sig. diff. in mean change in BMD (Chest 136:1456, 2009-JW).
    5. For postmenopausal women, consider supplements of Ca (1 - 1.5 g/d) and vit. D (400U/d)
  2. Concern for potential risk for pneumonia-not in one study in patients with COPD
    1. In a meta-analysis of data on over 7,000 pts with COPD who were randomized to inhaled budesonide vs. placebo for 6-12mos, there was no sig. diff. between the groups in incidence of pneumonia.  (Lancet 374:712, 2009-JW)
  1. Long-term effects of inhaled steroids on asthma
    1. In a study of over 7,000 pts 5-66yo with recent-onset asthma randomized to inhaled budesonide vs. placebo (200ug if < 11yo otherwise 400 ug/d); over 3y f/u, mean postbronchodilator FEV1 was minimally (1%) better in budesonide c/w placebo groups among adults; no sig. diff. in children ("SMART" Study; Chest 129:1478, 2006--JW)
  2. "Step approach" emphasizes downward titration to find minimum dose capable of maintaining control after control is achieved
  3. If a step up is needed; consider adding a long-acting beta-agonist (Salmeterol) rather than increasing dose of inhaled steroid (see below)
  4. Stepping down probably safe when sx are well-controlled
    1. In a randomized trial in 259 adults with persistent asthma on daily high-dose inhaled steroids, a program of tapering based on symptoms vs. continuing initial doses was ass'd, over 1y of f/u, with no sig. diff. in frequency of asthma exacerbations and hospital visits (BMJ 326:1115, 2003--JW)
  5. Advise pts to "rinse & spit" after use to prevent oral thrush
  6. Click on link for data on use of inhaled steroids in Managing Asthma Exacerbations

Specific inhaled corticosteroids:

Drug Strengths (per spray)
and dose
Notes
Beclosmethasone dipropionate (Qvar) 40mcg, 80mcg
1-4 puffs BID
 
Budesonide (Pulmicort) 90mcg, 180mcg
2 puffs BID
Also nebulized (0.25-0.5mg BID or 1mg QD in kids)
Ciclesonide (Alvesco) 80mcg, 160mcg
1-2 puffs BID
 
Mometasone (Asmanex) 110 mcg, 220 mcg
1 puff QD-BID
 
Flunisolide (Aerobid, Aerospan) 250 mcg
1-2 puffs BID
 
Fluticasone (Flovent Diskus and HFA) 50 mcg, 100 mcg, 250 mcg (diskus)
11-2 puffs BID
44 mcg, 110 mcg, 220 mcg (HFA)
2 puffs  BID
90% of efficacy achieved at 250ug/d; doses > 500ug/d
don't achieve any improvement in efficacy (BMJ 323:253,
2001--JW)

 

  1. Systemic Corticosteroids (prednisone, prednisolone, methylprednisolone)
  1. A last resort for maintenance: recc'd use for shortest time & lowest dose possible
  2. Periodically re-assess need for chronic systemic steroids
  3. 3pm dose may give better clinical results than am dose with no greater adverse f/x
  4. See under "Corticosteroids" for more information on dosing/avoiding side effects
  1. Mast Cell Stabilizers
  1. Reduce sx and improve lung function
  2. Can also use before predictable exposure to precipitants, e.g. exercise
  3. Excellent safety profile
  4. Allow 4-6 weeks for maximum benefit to appear
  5. OK to use as initial choice for long-term control in kids
  6. Probably less potent than inhaled steroids in kids: In a 1y randomized trial of 287 kids 2-6yo with persistent asthma randomized to cromolyn 20mg neb QID vs. budesonide neb 0.5mg QD x 8wks (then dose titration over the next 44wks), budesonide group had sig. lower mean exacerbations (1.23 vs. 2.41) and similar basal & ACTH-stimulated cortisol levels at 52wks BUT budesonide group grew sig. less than cromolyn group (mean diff. in height gain 0.86cm) (Ped. 109:866, 2002--JW)
  7. Specific agents
  1. Cromolyn 1-4 puffs (or 1 ampule (20mg) neb) TID-QID; same in kids; Neb may be more effective than MDI
  2. Nedocromil 1-4 puffs BID-QID; shown effective at BID dosing, recc'd QID; tastes worse than cromolyn
  1. Leukotriene modifiiers
  1. May be less effective than inhaled steroids
    1. Zafirlukast less effective than inhaled beclomethasone in a controlled trial (Eur. Resp. J. 10:419S, 1997--Med. Letter)
    2. 895 pts 15-85yo with persistent asthma randomized to montelukast 10mg HS, beclomethasone 200ug inhaled BID, or placebo. At 12wks, increase in FEV1 was sig. greater in beclomethasone group but no sig. diff. was seen in # of asthma exacerbations during the study period (Ann. Int. Med. 130:531, 1999--AFP)
    3. In a randomized trial of 533 adults & adolescents with persistent asthma randomized to fluticasone inhaled 88ug BID vs. montelukast 10mg QD (with corresponding placebos), over 24wk f/u, fluticasone group has sig. greater improvement in FEV1 and PEFR as well as sig. less use of albuterol and lower symptom scores (J. All. Clin. Immunol. 107:461, 2001--JW)
    4. In a systematic review of 13 randomized trial of leukotriene modifiers with inhaled steroids as monotherapy of mild-to-moderate persistent asthma, the former were ass'd with RR 1.6 for exacerbations requiring systemic corticosteroid therapy, and also had sig. less improvements in FEV1, sig. more use of short-acting bronchodilators, and fewer days without sx (BMJ 326:621, 2003--JW)
    5. In a study in 925 children 6-14yo with mild persistent asthma randomized to montelukast QD vs. fluticasone inhaled BID, at 1y, there was no sig. diff. in the primary outcome of asthma rescue-free days; fluticasone use was associated with sig. fewer days with beta-agonist use (12.8% vs. 15.4%), systemic corticosteroid use (10.5% vs. 17.8%, and % of pts with asthma attacks over the study period (25.6% vs. 32.2%) (Peds. 116:360, 2005--JW)
    6. In a study in 342 children 6-12yo with persistent asthma randomized to montelukast vs. inhaled fluticasone x 12wks, the fluticasone group had sig. higher incidence of > 5% improvement in FEV1 (10.6% vs. 4.6%) and sig. higher % of rescue-free days (45% vs. 35%) (J. Peds. 147:213, 2005--JW)
    7. In a study in 994 pts 6-14yo with mild persistent asthma randomized to montelukast QD vs. fluticasone inhaled BID x 1y, fluticasone was associated with nonsig. greater increases in mean FEV1, and incidence of asthma attacks were sig. greater in montelukast group (32.2% vs. 25.6%) (Peds. 116:493, 2005--AFP)
  1. Use in combination w/inhaled steroids may not offer significant benefit c/w placebo or salmeterol
    1. A systematic review of randomized trials of leukotriene modifiers vs. placebo were combined with inhaled steroids (BMJ 324:1545, 2002--JW) found that:
      1. 2 of 4 trials looking at risk for asthma exacerbations found LM's ass'd with nonsig. reduction
      2. 3 or 3 trials looking at dose of inhaled steroids found no benefit
      3. 4 of 4 trials looking at risk of pt withdrawals from the study due to poor asthma control showed sig. reductions
    2. 642 pts with asthma incompletely controlled with beclomethasone 200ug BID randomized to continued beclomethasone + montelukast 10mg QD vs. placebo + contrinued beclomethasone; over 16wk f/u, mean FEV1 was 5% higher with combined therapy than with beclomethasone alone; also improved sx scores with combined therapy (Am. J. Resp. Crit. Care Med. 160:1864, 1999--JW)
    3. 226 pts with asthma, all on BID inhaled steroids, randomized to Montelukast 10mg QD vs. placebo. The Montelukast group were more likely to be able to taper off steroids during the 12wk study period (BMJ 319:87, 1999--AFP)
    4. 1490 pts 15-72yo with asthma and FEV1 50-90% predicted despite use of inhaled steroids randomized to inhaled fluticasone + (montelukast or inhaled salmeterol).  At 48wks, improvements in sx and PFT's and likelihood of having had at least 1 asthma exacerbation were not sig. diff. between the two groups (BMJ 327:891, 2003--JW)
  1. Montelukast (Singulair) 5mg Qpm for 6-14yo; 10mg Qpm for > 14yo, or 2h before exercise
    1. A leukotriene receptor antagonist
    2. Unlike Zafirlukast & Zileuton, no reports of hepatotoxicity as of 1998 (Med. Letter 40:72, 1998)
    3. Also unlike those two, doesn't inhibit CYP-450 enzymes so no interactions with warfarin, digoxin, or theophylline.
    4. May cause a Churg-Strauss-like syndrome (vasculitis, peripheral eosinophilia, neuropathy, and cardiac complications)
    5. Comparison w/inhaled steroids: Unpublished study in package insert: Montelukast 10mg/d vs. beclomethasone 200ug BID produced less increase in FEV1 (Med. Lett. op. cit.)
    6. 366 children 6-14yo w/intermittent or persistent asthma randomized to 5mg montelukast HS vs. placebo over 8wks; 1/3 in each group were also using inhaled steroids; montelukast group had sig. increase in FEV1 c/w placebo group; no sig. adverse f/x noted. Also fewer exacerbations during study period w/monetlukast but no diff. in use of oral steroids (JAMA 279:1181, 1998)
    7. 681 pts > 15yo with intermittent or persistent asthma randomized to montelukast 10mg Qpm vs. placebo x 12wks; montelukast group had increased PEV1 c/w placebo and fewer nocturnal awakenings due to asthma and less use of quick-relief meds. Maximum tx effect seen within 24h of first dose.
    8. Reduces exercise-induced asthma c/w placebo (NEJM 339:147, 1998; J. Peds. 133:424, 1998--AFP)
    9. May be safe and effective for use in pts 2-5yo at dose of 4mg PO QD (Peds. 108:e48, 2001--JW)
  1. Zafirlukast (Accolate) 10mg BID for 5-11yo; 20mg BID for > 12yo (take at least 1h before or 2h after meals)
  1. A leukotriene receptor antagonist
  2. Adverse effects: GI disturbances, mild HA, increased transaminases. Rats given very high doses have increased incidence of hepatocellular adenoma, histiocytic sarcoma, and bladder Ca. May cause a Churg-Strauss-like syndrome (vasculitis, peripheral eosinophilia, neuropathy, and cardiac complications).
  3. Drug interactions: may potentiate warfarin, tolbutamide, phenytoin, carbamazepine, cyclosporine, astemizole, cisapride, dihydropyridine Ca-channel blockers
  4. More effective than placebo in children with exercise-induced bronchospasm (J. Peds. 134:273, 1999--JW)
  5. More effective than placebo in reducing sx and improving PFT's in pts with severe asthma (Chest 115:336, 1999--AFP)
  1. Zileuton (Zyflo) 1200mg BID for > 12yo only
  1. A 5-lipoxygenase inhibitor
  2. May cause hepatotoxicity
  1. 2-5% will get increase of SGPT to 3x normal
  2. Manufacturer reccs monitoring SGOT/SGPT before tx, Qmo x 3mos, Q2-3mos for 9 more mos, and "periodically thereafter"
  1. Female mice given 4x us. human doses x 2y had increased incidence of liver, kidney, and vasc. tumors
  2. Can cause dyspepsia
  3. May inhibit metabolism of terfenadine, warfarin, propanolol, and theophylline
  1. Long-acting beta-agonists (not helpful in acute exacerbations; make sure pts know this!)
  1. Specific agents
    1. Inhaled Salmeterol (Serevent) 1-2puffs Q12h; can use just QHS for nightly sx-Available in combination with fluticasone as "Advair"
    2. Inhaled Formoterol (Foradil) 1 puff Q12h-Available in combination with budesonide as "Symbicort"
    3. Inhaled Alformoterol (Brovana) inhalation solution, 15 micrograms BID
    4. Inhaled Indacaterol (Arcapta) 1 puff (75 mcg) once daily
    5. Oral albuterol (rarely used because of systemic side effects)
  2. Side f/x:
    1. Tachycardia, tremor, hypokalemia, hyperglycemia, QT prolongation with overdose; Tolerance may occur (Pediatrics 99:655, 1997-JW)
    2. In a meta-analysis of randomized trials of salmeterol 50ug BID vs. placebo in total 2,853 pts with COPD, no increased incidence of cardiovascular events was seen in salmeterol recipients.  (Chest 123:1817, 2003--AFP)
    3. Possible increase in risk of asthma exacerbations and  death from asthma
      1. In a study in 26,355 adolescents and adults with asthma (53% of whom were not on an inhaled steroid) randomized to inhaled salmeterol vs. placebo BID along with usual asthma meds, after 28wks, incidence of primary endpoint (respiratory death or intubation) was nonsig. higher in salmeterol group; in subgroup of pts who were African-American, the increase in risk was significant.  In overall cohort, incidence of asthma-related death was sig. greater in salmeterol recipients (the "SMART" study, Chest 129:15, 2006--JW)
      2. In a meta-analysis of 19 randomized studies of long-acting beta-agonists in > 30,000 children & adults, long-acting beta-agonists were associated with sig. increased risk for hospitalization for an asthma exacerbation (OR 2.6) and asthma-related death (OR 3.5) (Ann. Int. Med. 144:904, 2006--JW)
      3. FDA recommends against their use without another asthma "controller" medication-See: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm200931.htm
  3. Role in therapy-An adjunct, not a substitute for anti-inflammatory Rx
    1. In kids, salmeterol was inferior to low-dose inhaled beclomethasone in controlling asthma (less use of inhaled albuterol & oral prednisone; NEJM 337:1659, 1997--JW)
    2. 164 pts 12-65yo with persistent asthma randomized to inhaled salmeterol vs. triamcinolone vs. placebo after a 6wk run-in period of inhaled triamcinolone 400ug BID; over 16wk f/u, no diff. in sx BUT triamcinolone pts had sig. fewer tx failures (6% vs. 24%) and asthma exacerbations (7% vs. 20%) (JAMA 285:2583, 2001--JW, abst)
    3. The FDA added a "black-box" warning to long-acting beta-agonist medications that they should not be used as monotherapy for persistent asthma
  1. In adults, when inhaled steroids not controlling tx, may get better results adding salmeterol than with increasing steroid dose
  1. In patients with sx not controlled on Beclovent MDI 10 (500 mcg) puffs BID (maximum dose) plus prn Albuterol MDI, 24 weeks of adding Serevent (salmeterol) MDI 2 or 4 puffs BID was better than increasing dose of beclovent to 20 puffs (1000 mcg) BID, in terms of PEF, # of sx-free days; # of exacerbations, however, was similar in both groups (Am. J. Resp. Crit. Care Med 153:1481, 1996)
  2. 101 pts with mild-mod asthma also using inhaled steroids randomized to salmeterol 50ug BID vs. placebo; steroid intake adjusted according to sx and daily peak flows. Salmeterol group had 17% lower steroid use than placebo group and more sx-free days (82% vs. 64%); also greater porportion of days where they didn't have to use bronchodilators (73% vs. 58%); persisted through the 6mo trial period (BMJ 314:1441, 1997)
  3. In a meta-analysis of 9 randomized trials in 3685 pts or adding salmeterol vs. increasing steroid dose in pts with asthma incompletely controlled on inhaled steroids, addition of salmeterol was sig. superior in iterms of PEFR, FEV1, symptom control, and exacerbations (BMJ 320:1368, 2000--JW)
  4. In a study in 3,421 pts 12-80yo with inadequately-controlled persistent asthma randomized to salmeterol + fluticasone vs. fluticasone alone with doses tapered up to achieve control.  At 12wks, overall asthma control was sig. better in salmeterol-fluticasone group compared with the fluticasone-only group (Am. J. Resp. Crit. Care Med. 170:836, 2004--AFP)
  5. In a study in 210 adults with uncontrolled asthma on low-dose inhaled corticosteroids (beclomethasone 80ug BID) treated with 14wk courses of inhaled tiotropium, inhaled salmeterol, or doubling of the inhaled corticosteroid dose, both tiotropium and salmeterol were associated with sig. better improvements than doubled-corticosteroid dose in am peak flow, % of days where asthma was controlled, and daily symptom scores.  No sig. diff. between tiotropium and salmeterol.  (NEJM 9/19/2010-e-pub ahead of printing at: http://www.nejm.org/doi/full/10.1056/NEJMoa1008770-JW)
  1. Sustained-release Theophylline 0.2 (age in weeks) + 5 mg/kg/d in infants; 10-16mg/kg/d in children > 1yo; 300-600mg/d in adults
  1. Particularly for control of nocturnal sx in conjunction w/ inhaled steroids
  2. Side f/x: insomnia, stomach upset, GERD, hyperactivity, worsening of prostatism in males.
  3. Toxicity sx: tachycardia/tachyarrhythmias, n/v, headache, seizures, hyperglycemia, and hypokalemia
  4. Therapeutic serum concentrations 5-15 ug/ml; monitor levels
  5. Serum levels increased by cimetidine, macrolide and quinolone antibiotics; ticlopidine
  6. Elderly are more likely to have life-threatening side effects
  7. Avoid in pregnancy
  1. Omalizumab (Xolair) 150-300mg SQ Q4wks or 225-375mg SQ Q2-4wks (dosed according to body weight & serum IgE level)
    1. A recombinant monoclonal anti-IgE Ab--Binds to IgE in the bloodstream, preventing binding to mast cells & basophils
    2. Ass'd with isolated incidents of anaphylaxis
    3. Theoretically, lowering free IgE might increase risk of certain malignancies; studies as of 2005 have shown nonsig. increased incidence of malignancy with omalizumab vs. placebo
    4. Studies of clinical effectiveness
      1. In a randomized trial of 317 adolescents & adults w/asthma and at least 2 positive allergy skin tests, Omalizumab IV Q2wks x 20wks vs. placebo was ass'd with sig. reduced sx scores, corticosteroid use, and incidence of exacerbations. (NEJM 341:1966, 1999--JW; Med. Lett)
      2. In a randomized trial of 334 children 6-12yo with mod-to-severe asthma, all on inhaled steroids, omalizumab SQ Q2-4wks x 28wks ass'd with sig. higher rates of successful inhaled steroid w/d, fewer asthma exacerbations, and fewer missed school days than placebo. Adverse effects included urticaria and pruritis (Peds. 108:36, 2001--JW)
      3. A Cochrane meta-analysis of 8 randomized trials (cited in AFP 71:341, 2005) found that omalizumab use was ass'd with reduction of daily corticoseroid requirements, fewer exacerbations, and greater improvements in quality of life scores c/w placebo.
      4. In a study in 850 pts with asthma 12-75yo with inadequate symptoms control despite high-dose inhaled corticosteroids and long-acting beta-agonist treatment randomized to omalizumab vs. placebo, at 48wks the % of pts having had a serious asthma exacerbation was sig. lower in the omalizumab group (22% vs. 25%) (Ann. Int. Med. 154:573, 2011-JW)
  1. Others studied: Troleandromycin, cyclosporine, methotrexate, gold, IVIG, dapsone, and hydroxychloroquine. Recc'd for use only under supervision of an asthma specialist.
  2. Proton-Pump Inhibitors
    1. In a study in 306 pts 6-17yo with poorly-controlled asthma and no symptoms of gastroesophageal reflux randomized to lansoprazole vs. placebo x 6mos (all received inhaled corticosteroids), there were no sig. differences between the groups in asthma symptoms scores or measures of asthma control.  Of 115 children who underwent esophageal pH monitoring, 43% had asymptomatic GERD; this subgroup also did not have any benefit from lansoprazole.  However, lansoprazole recipients did have a sig. increased risk for upper respiratory infections during the study period (RR 1.3).  (JAMA 307:373, 2012-JW)