Si può desiderare di provare un trattamento naturale disfunzione erettile come un diverso per i problemi di costruzione. Al giorno d oggi ci sono diverse terapie sul mercato, ma un trattamento naturale disfunzione erettile è stato confermato qualche ora e ora di nuovo per dare risultati efficienti e permanenti. Cos è la disfunzione sessuale? L incapacità di sviluppare o sostenere una costruzione abbastanza lungo per fare l amore è chiamato disfunzione erettile, ED https://farmacia-senzaricetta.it/ o (maschio) problemi di erezione. Tutti gli uomini possono avere problemi di costruzione di volta in volta e gli scienziati considerano ED essere presenti se si verificano problemi di costruzione almeno il 25% del tempo. Alcuni fatti duri: ED Può essere dovuto a problemi emotivi. Stress, pressione, giltiness, depressione, bassa autostima e ansia prestazioni può essere la causa dei vostri problemi di costruzione. La ricerca ha confermato che il 90 per cento della disfunzione erettile è fisica in origine, non emotiva. L impotenza colpisce la maggior parte degli uomini durante la loro vita e può essere dovuto a troppo colesterolo, problemi cardiaci, diabete, ipertensione, fumo o alcol. Alcuni rimedi possono essere la ragione. Le questioni legate al movimento sono collegate. Se ti occupi dei tuoi problemi di movimento, hai piu possibilita di risolvere questo problema. Qui ci sono 5 consigli facili su come aumentare la circolazione: 1. Mangia i pasti giusti. Questo ti rendera il flusso sanguigno ovvio. Una grande parte di rimanere sani e anche mantenere il flusso sanguigno ovvio è legato al vostro piano di alimentazione quotidiana e quello che si mangia. Una buona cura per la disfunzione erettile è mangiare un piano a basso contenuto di grassi e grande alimentazione di fibre. Mangiare fibre tutti i giorni e questo viene scoperto in prodotti cerealicoli cereali integrali, frutta e verdura. Evitare il più possibile pasti pronti o pasti non sani. 2. Wonder herbal rimedi. Molti rimedi vegetali per ED eseguire bene come possono migliorare il movimento. Hanno molto meno reazioni avverse rispetto ai farmaci convenzionali e si svolgono in modo efficiente per migliorare hardons e la forza, troppo. Erbe naturali come Ginkgo Biloba sono utilizzati come una strategia per ED. Gli specialisti di erboristeria credono anche che le spezie o le erbe come noce moscata, portano al movimento intorno al corpo, tra cui il pene. 3. Vitamine naturali vitali. Gli scienziati sanitari hanno scoperto che una mancanza di supplemento è tipico tra gli uomini con ED in particolare vitamina A. Se si ha una mancanza del nutriente ossido di zinco, Questo è stato confermato per portare alla disfunzione erettile. Queste inadeguatezze derivano dal fatto che molti valori nutrizionali in quello che mangiamo piano non sono sufficienti. Aggiungere al vostro fabbisogno di nutrienti aumenterà la circolazione del sistema e migliorare questa condizione. Gli integratori alimentari sono completamente naturali, quindi non dovrete preoccuparvi dei rischi di reazioni avverse. Inoltre, queste vitamine naturali sono utili per il vostro benessere over-all. Oltre a questi vantaggi benessere, disfunzione erettile vitamine naturali e integratori costano molto meno di farmaci rimedi. 4. Esercitare. Fai una mossa e non un tablet vibrante. Camminare farà di più per migliorare e sostenere hardons di qualsiasi altra compressa chimica nel lungo periodo. Il fitness fisico manterrà bassi livelli di pressione e mantenere grandi stadi di movimento. Andando per un 20-30 minuti di movimento rapido ogni giorno, può affrontare questo problema e può sostenere la vostra libido senza l uso di qualsiasi farmaco. 5. Sottolineare. Questo è il peggior attaccante per problemi di erezione. Scopri diversi metodi per riposare. Alcuni metodi tipici per riposare includono la lettura di un libro, la meditazione, un bagno rilassante o allenamenti di respirazione. Sto solo imparando alcuni semplici allenamenti di respirazione che possono migliorare significativamente il movimento nel reparto pantaloni. Una naturale disfunzione erettile soluzioni di trattamento stanno diventando sempre più popolare con gli uomini. Questi rimedi a base di erbe sono preferiti perché non hanno reazioni avverse e sono confermati essere efficiente come il farmaco. La maggior parte degli uomini combattere parlano dei loro problemi, in particolare la disfunzione erettile come c è poca discussione sui problemi di erezione. La verita e che ED ha un impatto su piu di dieci milioni di uomini solo negli Stati Uniti. Non siete soli e l aiuto è disponibile.
Randmalonemd.com
The safety of twice-daily treatment with fluticasone propionate and salmeterol in pediatric patients with persistent asthma Randolph Malone, MD*; Craig LaForce, MD†; Sai Nimmagadda, MD‡; Lynne Schoaf, RN§; Karen House, MS§; Anna Ellsworth, BS§; and Paul Dorinsky, MD§ Background: For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid (ICS)
therapy, the preferred treatment is to add an inhaled long-acting  -agonist vs increasing the ICS dose. Objective: To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting
 -agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma. Methods: A randomized, multicenter, double-blind, active-controlled, parallel-group study in 203 children with persistent
asthma who were symptomatic during ICS therapy. Patients received fluticasone propionate–salmeterol (100/50 g) orfluticasone propionate (100 g) alone twice daily for 12 weeks. Results: The safety profile of fluticasone propionate–salmeterol was similar to that of fluticasone propionate alone. The overall
incidence of adverse events was 59% for fluticasone propionate–salmeterol and 57% for fluticasone propionate. Both treatmentswere well tolerated. Two patients receiving fluticasone propionate–salmeterol and 5 receiving fluticasone propionate withdrewfrom the study because of worsening asthma. Changes in heart rate, blood pressure, and laboratory variables were infrequent andwere similar between treatments. No patients had clinically significant abnormal electrocardiographic findings during treatment. Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within andbetween groups; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment. The incidence of withdrawals due to asthma exacerbations was 2% in the fluticasone propionate–salmeterol group and 5% in thefluticasone propionate group. Conclusions: In pediatric patients with persistent asthma, fluticasone propionate–salmeterol twice daily was well tolerated,
with a safety profile similar to that of fluticasone propionate used alone. Ann Allergy Asthma Immunol. 2005;95:66–71. INTRODUCTION
the preferred treatment for initiating therapy in children of all
Asthma is the most common chronic disorder in children and
ages with persistent asthma.3 For children older than 5 years
adolescents.1 In 1999, more than 3.1 million children younger
who remain symptomatic despite treatment with low-dose
than 15 years in the United States had an episode of asthma
ICSs, the guidelines indicate that the preferred treatment is
or an asthma attack in the preceding 12 months.2 During this
the addition of an inhaled long-acting  -agonist to the ICS
same period, asthma was responsible for 190,000 hospital-
rather than an increase in the dose of ICS.3 This therapeutic
izations and 658,000 emergency department visits.2 Asthma
approach helps ensure use of the lowest effective dose of ICS,
also has a considerable effect on school attendance, account-
thereby minimizing the potential for systemic adverse effects.
ing for 14 million missed school days from 1994 to 1996.2
Given the substantial morbidity of pediatric asthma and the
The substantial morbidity of asthma in children suggests that
current treatment guideline recommendations, this study was
additional therapies and treatment strategies are needed.
conducted to compare the safety of twice-daily fluticasone
Expert panel guidelines by the National Heart, Lung, and
propionate–salmeterol (100/50 g) with that of twice-daily
Blood Institute recognize inhaled corticosteroids (ICSs) as
fluticasone propionate (100 g) alone in children 4 to 11years of age with persistent asthma. Safety measures includedadverse events, clinical laboratory tests, 24-hour urinary cor-tisol excretion, 12-lead electrocardiograms (ECGs), vital
* Southeast Asthma and Allergy Center, Tallahassee, Florida.
signs, oropharyngeal examinations, and asthma exacerbations
† North Carolina Clinical Research, Raleigh, North Carolina. ‡ Associated Allergists and Asthma Specialists Ltd, Hoffman Estates, Illi-
nois. § GlaxoSmithKline, Research Triangle Park, North Carolina.
This study was funded by GlaxoSmithKline, Research Triangle Park, NC. This study was presented in part at the American College of Asthma, Allergy
and Immunology 2003 Annual Meeting; November 8 and 9, 2003; New
Boys and premenarchal girls aged 4 to 11 years were eligible
Orleans, LA; and at the American College of Chest Physicians Annual
for this study if they had asthma, as defined by the American
Meeting; October 27, 2004; Seattle, WA.
Thoracic Society criteria,4 for at least 2 months and were
Received for publication December 6, 2004. Accepted for publication in revised form February 9, 2005.
receiving ICS therapy (beclomethasone dipropionate, 252–
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
336 g/d; triamcinolone acetonide, 600 –1,000 g/d; fluni-
tom score of at least 1 (on a scale from 0 to 5) on 3 or more
solide, 1,000 g/d; fluticasone propionate, 88 –250 g/d; or
days or the use of albuterol on 3 or more days during the 7
budesonide, 200 – 400 g/d) at a consistent dose for at least 1
days before the randomization visit, and (3) adequate com-
month before screening. At the screening visit, patients aged
pliance, defined as 70% or greater compliance with diary card
6 to 11 years were required to have a forced expiratory
volume in 1 second (FEV ) of 50% to 95% of the Polgar
Patients returned to the clinic after 1, 2, 4, 8, and 12 weeks
predicted value5; patients aged 4 to 5 years were required to
of treatment. In addition, each patient’s parent or guardian
have a morning peak expiratory flow rate (PEFR) of 50% to
was contacted 3 to 5 days after the final visit for evaluation of
95% of the Polgar predicted value.5 Patients were also re-
posttreatment adverse events. Parents or guardians recorded
quired to demonstrate an increase in FEV (for patients aged
morning and evening PEFRs, use of albuterol for relief of
6 –11 years) or morning PEFR (for patients aged 4 –5 years)
symptoms, and daytime asthma symptom scores on a daily
of 12% or more within 30 minutes of inhalation of 2 to 4
diary card. Symptom scores were based on a Likert scale
actuations of albuterol (180 –360 g) or to have historical
from 0 (no symptoms) to 5 (severe symptoms that prevented
documentation of 12% or greater reversibility within the
normal daily activities). Morning and evening PEFRs were
measured before taking a dose of study medication or albu-
Exclusion criteria consisted of a history of life-threatening
asthma; hospitalization due to asthma twice or more in the
previous year; a significant concurrent disease (eg, cysticfibrosis, malignancy, or immunologic compromise); recent
At the end of the run-in period, eligible patients discontinued
upper or lower respiratory tract infection; current chickenpox
their current ICS therapy and were randomly assigned to
or recent exposure to chickenpox in a nonimmune patient;
receive 1 of the following blinded treatments twice daily for
severe milk protein allergy; hypersensitivity to  -agonist,
12 weeks: fluticasone propionate–salmeterol, 100/50 g (Ad-
sympathomimetic, or corticosteroid therapy; clinically signif-
vair Diskus; GlaxoSmithKline, Research Triangle Park, NC),
icant abnormal laboratory test results; a history or present use
or fluticasone propionate, 100 g (Flovent Diskus; Glaxo-
of tobacco; and a history or current presence of glaucoma or
SmithKline). Patients were assigned to treatment in accor-
posterior subcapsular cataracts. Patients were required not to
dance with a predetermined randomization schedule and ad-
have used oral or parenteral corticosteroids for at least 1
ministered 1 inhalation from the Diskus each morning and
month before screening, cromolyn or nedocromil for at least
evening, approximately 12 hours apart.
1 week before screening, or long-acting  -agonists within 48
hours of screening and throughout the study. In addition, the
Adverse events were monitored throughout the study, and
use of medications that could affect the course of asthma or
investigators were responsible for the detection, documenta-
interact with study medications (eg, anticholinergics, anticon-
tion, intensity evaluation, and causality evaluation of all
vulsants, or -adrenergic blockers) was prohibited through-
adverse events. Routine clinical laboratory evaluations were
performed after an overnight fast at screening and after 12
weeks of treatment or at study discontinuation. Threshold
This randomized, multicenter, double-blind, active-con-
ranges for each laboratory variable were defined a priori as a
trolled, parallel-group study was conducted on an outpatient
measure of abnormalities of potential clinical concern. A
basis at 66 sites in the United States and 13 sites in Canada
timed 24-hour urine collection for cortisol excretion was
between April 2002 and January 2003. An institutional re-
conducted within 7 days of randomization and within 7 days
view board approved the study protocol, and informed con-
of the week 12 visit. A 12-lead ECG was also recorded at
sent was obtained for all patients before enrollment. Eligible
screening, randomization, and after 12 weeks of treatment or
patients underwent physical examinations, pulmonary func-
at study discontinuation. An independent cardiologist,
tion testing, and other screening procedures and then entered
blinded to treatment assignment, interpreted all ECGs at-
a 2-week run-in period, during which their baseline ICS
tained in the study. Vital signs (ie, systolic and diastolic blood
therapy was continued. All patients were also supplied with
pressure) and physical examination findings were recorded at
an albuterol metered-dose inhaler for rescue use. During this
screening and after 12 weeks of treatment or at study discon-
period, we evaluated the patient’s eligibility for randomiza-
tinuation. An oropharyngeal examination for clinical evi-
tion and compliance with the study procedures and attained a
dence of infection (eg, Candida albicans) was conducted at
baseline for safety measures. Patients who completed the
all study visits. If evidence of infection was found, a culture
run-in period and met all the randomization criteria pro-
was taken and appropriate therapy was instituted.
ceeded to the double-blind treatment period. Randomization
Asthma exacerbations or worsening asthma was also eval-
criteria included (1) a morning FEV of 50% to 95% of the
uated throughout the study. Patients were withdrawn from the
Polgar predicted value for patients 6 to 11 years of age or a
study because of worsening asthma if they experienced a
morning PEFR of 50% to 95% of the Polgar predicted value
clinical exacerbation or at the investigator’s discretion. A
for patients 4 to 5 years of age, (2) a daytime asthma symp-
clinical exacerbation was defined as worsening asthma that
required emergency intervention, hospitalization, or treat-
failure to meet FEV or PEFR percent predicted entry criteria
ment with an asthma medication prohibited by the protocol.
at the screening visit. Randomization resulted in comparable
The following criteria were used to aid the investigator in
treatment groups at baseline with respect to patient demo-
determining asthma stability: a 20% or greater decrease from
graphics and pulmonary function (Table 1). Fluticasone pro-
the best FEV obtained at the randomization visit for patients
pionate was the most commonly used ICS before randomiza-
aged 6 to 11 years, more than 3 of 7 days immediately
tion in each treatment group (Table 1).
preceding a study visit in which the morning or evening
Mean overall compliance with study medication was 93%
PEFR decreased 20% or more from the mean morning base-
for the fluticasone propionate–salmeterol group and 89% for
line PEFR calculated for the 7 days before the randomizationvisit, or more than 2 of 7 days immediately preceding a studyvisit in which 12 or more puffs per day of albuterol were
Table 1. Patient Characteristics at Baseline (Treatment Day 1)
used. These criteria were used as a guideline but did not
Fluticasone
require that a patient be withdrawn from the study. Compli-
Fluticasone propionate–
ance with study medication was calculated for each patient
propionate salmeterol
based on the dose counter on the Diskus. (n؍102) (n؍101)
Although this study was a safety study and was not designed
to evaluate efficacy differences between treatment groups,
the following assessments were performed: 2-hour serial
postdose FEV (for patients aged 6 –11 years) or 2-hour serial
postdose PEFR (for patients aged 4 –5 years) after the first
dose of study medication on treatment day 1, FEV (for
patients aged 6 –11 years only), morning and evening PEFRs,
and daytime asthma symptom scores and 24-hour albuterol use.
Because this was a safety study, no primary end point was
identified; thus, no power calculations were performed. How-
ever, it was estimated that approximately 100 patients in each
treatment arm was sufficient to evaluate the safety of fluti-
casone propionate–salmeterol compared with fluticasone pro-
pionate. The intent-to-treat population, which included all
patients who were randomized and received at least 1 dose of
study drug, was the primary population used for all demo-
graphic and safety measures except for cortisol excretion. For
patients who withdrew from the study prematurely, all avail-
able data up to the time of discontinuation were included in
the intent-to-treat population. The cortisol population, the
primary population for urinary cortisol analyses, was defined
as the intent-to-treat population excluding patients with 1 or
more of the following: urine volume less than 300 mL (for
patients aged 4 –5 years) or less than 400 mL (for patients
aged 6 –11 years) and 24-hour creatinine excretion below a
predefined threshold range; a collection time that was not less
than 24 Ϯ 4 hours in duration; oral, parenteral, or topical
(Ն1% hydrocortisone) corticosteroid use within 30 days of
visit 1 or during the study; not taking the study drug for more
than 1 day before the start of urine collection; and failure to
have both a baseline and a posttreatment urine collection.
Urinary cortisol excretion values were not corrected for cre-
Abbreviations: CFC, chlorofluorocarbon; FEV , forced expiratory vol-
ume in 1 second; HFA, hydrofluoroalkane; ICS, inhaled corticosteroid;NA, not applicable; PEFR, peak expiratory flow rate.
* Reversibility was evaluated at screening.
Of 421 children screened, 203 (48%) were randomly assigned
† The toal daily dose of ICS was calculable in 93 patients in the
to receive treatment. The most common reasons for excluding
fluticasone propionate–salmeterol group and in 89 patients in the
patients before randomization were lack of reversibility and
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
the fluticasone propionate group. The mean number of days
gastrointestinal discomfort and pain, nausea and vomiting,
that patients received treatment was 74.8 and 78.8 in the
and fever. Thirteen percent of patients treated with flutica-
fluticasone propionate–salmeterol and fluticasone propionate
sone propionate–salmeterol and 9% treated with fluticasone
groups, respectively. A total of 81% and 84% of patients in
propionate experienced at least 1 adverse event during the
the fluticasone propionate–salmeterol and fluticasone propi-
study that was considered by the investigator to be potentially
onate groups, respectively, completed the study.
related to treatment (drug related). The most common drug-
related adverse events for the fluticasone propionate–salme-terol and fluticasone propionate groups included headaches
One patient experienced a serious adverse event (asthmaexacerbation) during the run-in period. This patient was dis-
(Ͻ1% and 4%), candidiasis of the mouth or throat (4% and
continued from the study and was not randomized to receive
0%), throat irritation (3% and 2%), dizziness (2% and Ͻ1%),
double-blind study medication. Both treatments were well
tolerated during the 12-week study. The overall incidence of
Three patients treated with fluticasone propionate–salmet-
adverse events was similar in the 2 groups (59% for flutica-
erol experienced adverse events that led to premature with-
sone propionate–salmeterol and 57% for fluticasone propi-
drawal from the study. One of these patients experienced
onate) (Table 2). The most common adverse events included
angioedema and hives that were not considered to be drug
headache, upper respiratory tract infection, throat irritation,
related. Another patient experienced chest pain, which wasconsidered to be drug related, and shortness of breath, whichwas not considered to be drug related. The third patient
Table 2. Adverse Events During Treatment*
experienced sleeplessness (for 38 days) during treatment thatwas considered to be drug related. None of the patients
Fluticasone Fluticasone propionate–
treated with fluticasone propionate were withdrawn from the
propionate salmeterol
study prematurely because of adverse events. (n؍102) (n؍101)
For most patients treated with fluticasone propionate–salme-
terol or fluticasone propionate, hematology and chemistry
values were normal and fell within the predefined threshold
ranges for the following analytes: hemoglobin, hematocrit,
red blood cells, white blood cells, neutrophils, lymphocytes,
monocytes, eosinophils, basophils, platelets, alkaline phos-
phatase, alanine aminotransferase, aspartate aminotransfer-
ase, total bilirubin, creatinine, glucose, calcium, potassium,
sodium, urea nitrogen, total protein, and albumin. Three
patients in each treatment group had clinical laboratory val-
ues that were outside the threshold ranges. For the fluticasone
propionate–salmeterol group, 1 patient had a decrease in
elevation in glucose level (from 112 to 155 mg/dL), and 1 had
an elevation in potassium level (from 4.6 to 6.8 mEq/L,
which normalized on repeated measurement to 4.4 mEq/L).
For the fluticasone propionate group, 1 patient had a low
neutrophil count at baseline that further decreased after treat-
ment (from 1.3 to 0.78 ϫ 103/L), 1 had a high eosinophil
count at baseline that further increased after treatment (from
ϫ 103/L), and 1 had an increase in glucose level
24-Hour Urinary Cortisol Excretion
A total of 48 and 57 patients in the fluticasone propionate–
salmeterol and fluticasone propionate groups, respectively,
were included in the cortisol population. Geometric meanurinary cortisol excretion at baseline was comparable be-
Abbreviation: FEV , forced expiratory volume in 1 second.
tween treatment groups (fluticasone propionate–salmeterol
* Data are given as percentage of patients.
† Includes all events (whether considered drug related or not drug
g/24 hours; fluticasone propionate group: 7.82
related by the investigator) that occurred at a rate of 3% or greater in
g/24 hours). At treatment week 12, geometric mean urinary
cortisol excretion was 10.29 g/24 hours in the fluticasone
propionate–salmeterol group compared with 7.37 g/24
improvements in FEV 6 and in morning and evening PEFRs
hours in the fluticasone propionate group. The geometric
during treatment with fluticasone propionate–salmeterol
mean ratio for urinary cortisol excretion (week 12– baseline)
compared with fluticasone propionate alone.
was 1.26 for patients treated with fluticasone propionate–salmeterol compared with 0.94 for those treated with flutica-
DISCUSSION
sone propionate alone. Although all patients were receiving
The results of this clinical study demonstrate that treatment
ICS on study entry, none in either group had urinary cortisol
with fluticasone propionate–salmeterol for 12 weeks had a
excretion values that were below the reference range (1.4 –18
safety profile similar to that of treatment with fluticasone
g/24 hours for patients aged 4–6 years, 1.6–21 g/24 hours
propionate alone. Both treatments were well tolerated, with
for patients aged 7–10 years, and 2.1–38 g/24 hours for
no serious drug-related adverse events reported in either
patients aged 11 years) after 12 weeks of treatment in this
group. Changes in heart rate, blood pressure, and laboratory
variables were infrequent and were similar between treatmentgroups, and no patient had a clinically significant abnormal
ECG finding during treatment. No patient in either group had
For all patients in both treatment groups, all baseline ECGs
evidence of hypothalamic-pituitary-adrenal axis suppression
were within the reference limits or were not considered
as evaluated by 24-hour urinary cortisol excretion. Specifi-
clinically significantly abnormal. After 12 weeks of treatment
cally, geometric mean urinary cortisol excretion at baseline
or premature study discontinuation, none of the patients in
and after 12 weeks of treatment was comparable within and
either treatment group had clinically significant abnormal
between groups. Furthermore, none of the patients in either
ECG findings. In addition, mean heart rate and QTc intervals
treatment group had a value for 24-hour urinary cortisol
were similar between the treatment groups after 12 weeks of
excretion that was below the lower limit of the reference
treatment and were comparable to baseline values. After 12
range after 12 weeks of treatment in this study. Finally, the
weeks of treatment, the mean heart rate was 79.3/min in the
incidence of withdrawals due to asthma exacerbations was
fluticasone propionate–salmeterol group and 78.7/min in the
lower in the fluticasone propionate–salmeterol group than in
fluticasone propionate group. The mean QTc interval was
the fluticasone propionate group (2% vs 5%).
313.8 milliseconds in the fluticasone propionate–salmeterol
Current guidelines in children and adults recommend the
group and 327.3 milliseconds in the fluticasone propionate
use of inhaled long-acting  -agonists plus ICS as the pre-
ferred therapy for patients with persistent asthma who remain
Mean systolic and diastolic blood pressures were compa-
symptomatic while receiving ICS treatment, thus helping to
rable between treatment groups at screening and throughout
ensure that the lowest effective dose of ICS is used.3 For
the study. Mean changes from baseline in systolic or diastolic
pediatric patients who remain symptomatic while receiving
blood pressure were small and comparable within and be-
an ICS, treatment options are limited and include increasing
the dose of ICS, adding an agent such as salmeterol, oradministering oral corticosteroids. In this regard, salmeterol
has been previously shown to be effective in patients older
Oropharyngeal candidiasis occurred in 4 patients treated with
than 4 years with asthma.7,8 In addition, treatment with flu-
fluticasone propionate–salmeterol and in none treated with
ticasone propionate–salmeterol, 100/50 g, twice daily via
Diskus has been previously shown to be as safe and effective
Asthma Exacerbations and Worsening Asthma
as fluticasone propionate, 100 g, and salmeterol, 50 g,
The incidence of asthma exacerbations and withdrawals due
administered concurrently twice daily in patients aged 4 to 11
to worsening asthma were lower in the group treated with
fluticasone propionate–salmeterol vs fluticasone propionate
The addition of salmeterol to an ICS represents a treatment
alone. Asthma exacerbations occurred in 3 patients (3%)
option for patients who remain symptomatic while taking an
treated with fluticasone propionate–salmeterol and in 8 pa-
ICS that minimizes the risk of systemic effects that can occur
tients (8%) treated with fluticasone propionate. Two patients
when either higher doses of ICSs or oral corticosteroids are
(2%) treated with fluticasone propionate–salmeterol and 5
administered. Unlike all other potential treatment options for
patients (5%) treated with fluticasone propionate were with-
patients who remain symptomatic while receiving an ICS, the
drawn from the study because of asthma exacerbations.
use of a long-acting  -agonist with an ICS in a single device
eliminates the possibility that patients can selectively discon-
This study was a safety study and was not designed to
Therapy with an ICS and a long-acting  -agonist ad-
evaluate efficacy differences between treatment groups.
dresses inflammation and smooth muscle dysfunction (eg,
However, as noted previously, some measures of efficacy
bronchoconstriction), the 2 main components of asthma. In
were obtained in this study. In this regard, although daytime
addition, salmeterol possesses several nonbronchodilator
asthma symptom scores and albuterol use improved to a
properties that may contribute to its therapeutic effects. For
similar degree in both groups, there were numerically greater
example, salmeterol has demonstrated inhibitory effects on
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
vascular permeability,10–12 platlet-activating factor–induced
2. Mannino DM, Homa DM, Akinbami LJ, Moorman JE, Gwynn
eosinophil accumulation,8,13 and the release of mast cell me-
C, Redd SC. Surveillance for asthma—United States,
diators from the lung.10,14,15 Salmeterol has also demonstrated
1980 –1999. MMWR Surveill Summ. 2002;51:1–13.
the ability to prime the glucocorticoid receptor for activation
3. National Asthma Education and Prevention Program. Expert
Panel Report: Guidelines for the Diagnosis and Management of
by corticosteroids16; however, the clinical relevance of these
Asthma. Update on Selected Topics—2002. J Allergy Clin
in vitro observations is unclear. These findings suggest that
Immunol. 2002;110:S141–S219.
using an ICS with a long-acting  -agonists has a broad scope
4. American Thoracic Society. Standards for the diagnosis and
of activity in the treatment of asthma.
care of patients with chronic obstructive pulmonary disease
In summary, the results of this clinical trial demonstrate
(COPD) and asthma. Am Rev Respir Dis. 1987;136:225–244.
that treatment for 12 weeks with fluticasone propionate–
5. Polgar G, Promadhat V. Pulmonary Function Testing in
salmeterol, 100/50 g, twice daily was well tolerated in
Children: Techniques and Standards. Philadelphia, PA: WB
children aged 4 to 11 years with persistent asthma and has a
safety profile that is similar to that of fluticasone propionate,
6. House K, Dorinsky PM, Stauffer J, Schoaf L, Ellsworth A. The
100 g, twice daily alone. In addition, the use of salmeterol
safety of fluticasone propionate/salmeterol Diskus in pediatricpatients ages 4 –11 with asthma [abstract]. Chest. 2004;126:
with an ICS represents a treatment option for patients who
remain symptomatic while taking an ICS that minimizes the
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