Document 6427517

Tuesday, October 28, 1997
Issues in Airway Inflammation, continued
PULMONARY INVOLVEMENT IN INFLAMMATORY BOWEL
DISEASE
Carlo Lombardi, MD, FCCP; MA Vitto, MD*; P Cesari, MD.
Unit and *Gastroenterologic Section, Dept. of Inter¬
Pneumoallergologic
nal Medicine, Sant' Orsola Hospital, Brescia, Italy
Purpose: Respiratory involvement in patients with inflammatory bowel
disease (IBD) has been reported mainly since 1976. This form of
extraintestinal manifestation should clearly be separated from interstitial
disease due to sulfasalazine or mesalamine. A variety of respiratory
lung
disorders have been described including pulmonary vasculitis and apical
fibrosis. Bronchial involvement (chronic suppurative bronchitis, bronchi¬
ectasis) have been noted.
We report the data of 46 consecutive patients (M:26; F:20; mean age:
40.6 yrs; onset of IBD:9.0 yrs) with ulcerative colitis observed in our
who developed varied bronchopulmonary problems.
Hospital
Results: In most cases bronchopulmonary involvement followed the
onset of IBD. Respiratory involvement could be grouped into 3 clinico¬
disease: chronic bronchitis, asthma,
pathologic categories: (1) airway
bronchiectasis; (2) serositis; (3) interstitial lung disease. Smoke exposure
was seen in 21.7% of patients. IBD therapy was taken in 53% of patients.
Conclusions: We observed a high prevalence of bronchopulmonary
diseases in ulcerative colitis.
Clinical Implications: These findings suggest that in patients with
ulcerative colitis the pulmonary involvement may be important.
EFFECT OF INHALED NEDOCROMIL OR BUDESONIDE OR
IN COMBINATION ON BHR IN COUGH ASTHMATICS
Seung Hyug Moon, MD, YH Kim, MD, HT Kim, MD, SY Ki, MD,
SW Jung, MD, CS Park, MD.Dept. of Internal Medicine. Soonchunhyang Univ. College of Medicine, Chunan, Korea
Purpose: To evaluate the time course of BHR and 'symptom score'
to a different inhaled anti-inflammatory therapeutic modalities,
according
and an efficacy of nedocromil and its synergistic effect on inhaled
budesonide in cough asthmatics, and the parameters which impact on the
therapeutic
response of BHR in cough asthma.
Patients and Methods: A prospective study for investigation the time
course of BHR and symptom score in 54 cough asthmatics was performed.
22 patients entered the budesonide (400 |xgX2/d), 17 entered the
nedocromil (4 mgX2/d), and 15 entered combined group. The BHR was
estimated by PD20 via methacholline challenge test using counted breath
method. The symptom was estimated by symptom score. Reevaluation of
BHR and symptom score was performed at 8 wks after inhaled treatment,
and if PD20 was not normalized at this time, follow-up of that was
at 16- and/or 24-wks after inhaled treatment.
performed
Results: The percentage of patients with normalized PD20 after 8 wks
treatment was not different in each group (p=0.57). The improvement of
BHR and symptom score in patients with not-normalized PD20 at 8 wks
in each group was significantly increased (p<0.05), but there was no
significant change of BHR during follow-up 16- and 24-wks after treat¬
ment (p>0.05). There was no significant difference in the degree of
percent increase of BHR in each group (p>0.05). In comparison of
allergic markers, such as serum IgE, peripheral eosinophil count, and skin
test reactivity between normalized and not-normalized after 8 wks
treatment, there was no significant difference in each other (p>0.05). In
symptom duration, age, and initial PD20 value, there was a significant
difference in each other (p<0.05).
Conclusions: The response to use of a combination of inhaled
budesonide and nedocromil for the treatment of cough asthmatics is not
superior to that achieved by either of these agents used alone.
Clinical Implications: Either inhaled budesonide or nedocromil alone
can be effective as a therapeutic modality on cough asthma.
LARGE AIRWAY DISEASE ASSOCIATED WITH INFLAMMA¬
TORY BOWEL DISEASE
Avrum Spira, MD; R Grossman, MD, FCCP; M Baiter, MD, FCCP.
Mount Sinai Hospital, Toronto, Ontario, Canada
Methods: We reviewed the cases of seven IBD patients who were
referred to the respirology department at a tertiary care hospital with new,
and unexplained symptoms of respiratory disease.
persistent
Results: The presenting respiratory complaint in all 7 patients was a
chronic productive cough. The onset of respiratory symptoms followed the
diagnosis of IBD by an average of 12 years (range, 3 months to 35 years).
patients were ultimately diagnosed via computed tomography (CT)
of the chest with bronchiectasis, while the remaining 2 were
with chronic bronchitis. 5 patients were non-smokers and only
diagnosed
one of the remaining two patients had a significant smoking history. None
of the patients had a significant history of childhood pneumonia or other
or gastroesophageal reflux. Bronchoscopy was
lung disease,on sinusitis
4 patients and was unremarkable in all but one who
performed
demonstrated airway inflammation. Sputum and bronchoalveolar lavage
cultures were negative, except in 2 patients who grew Haemophilus
Three patients were given therapeutic trials of oral steroids,
infiuenzae.
and all experienced a dramatic improvement in their cough.
Conclusion: Chronic bronchitis and bronchiectasis are rare pulmonary
that should be considered in IBD patients devel¬
complications of IBD and
oping new, persistent unexplained respiratory symptoms, particularly
chronic productive cough.
Chnical Implications: IBD patients developing new respiratory symp¬
toms may warrant early work up for large airway disease (with CT scan
and pulmonary function tests), along with a therapeutic trial of oral
steroids. The precise incidence of IBD-associated lung disease is currently
Five
scan
being investigated prospectively in our institution.
Issues in Asthma
MANAGEMENT OF STEROID-DEPENDENT ASTHMA WITH
METHOTREXATE: A META-ANALYSIS OF RANDOMIZED
CLINICAL TRIALS
Shawn D Aaron, MD; RE Dales, MD; B Pham.Ottawa General
Hospital, University of Ottawa, Ottawa, Canada
determine whether methotrexate is an effective steroidObjective: To
for
with severe asthma.
sparing
agent
Data
patients
Sources: Published reports of controlled trials assessing the use
of methotrexate in asthma were identified by a search of the MEDLINE,
EMBASE, and Current Contents databases. Bibliographies from identi¬
fied studies and from review articles were manually searched. Published
and unpublished reports in any language were identified and assessed for
inclusion in the meta-analysis.
Study Selection: Randomized, double-blinded, placebo-controlled
trials in which low-dose methotrexate was administered to corticosteroidand oral steroids were subsequently tapered
dependanttoasthmatics,
the patients' clinical status.
according
Data Extraction: Data were extracted independently by two review¬
ers. For all eligible trials, the mean reduction in oral corticosteroid dose,
the mean change in FEVl5 and the standard deviations, were calculated
for the treatment and control groups. Data concerning side effects of
were also extracted.
therapy
Data Synthesis: Data from 12 studies, reporting on a total of 250
patients, were pooled using a weighted average method, with weights
of the variance of the treatment effect.
proportionalto to the inverse
the use of methotrexate was associated with a
Compared
placebo,
6.0% improvement in FEVX (95% CI, 1.0% to 11%) and an 18.2%
pooled
reduction in oral steroid use (95% CI, 11.7% to 24.7%). This corre¬
to a 3.3 mg/day greater reduction in oral steroid use for patients
spondedmethotrexate
than for those taking placebo (95% CI, 2.1 to 4.4
taking This estimate was
when parallel studies were analysed
mg/d). from crossover unchanged
studies in a sensitivity analysis. Minor gastroin¬
separately
testinal complications and transient increases in liver enzymes were more
common in patients randomized to methotrexate. Three potentially
side-effects (2 pneumonias and 1 liver dysfunction)
life-threatening
occurred in 159 patients randomized to methotrexate vs. none in those
patients on placebo.
Purpose: Lung disease is a rare complication of inflammatory bowel
disease (IBD). We report a series of 7 patients with IBD who subse¬
quently developed large airway disease of unexplained etiology.
Conclusions: Methotrexate allowed a modest reduction in oral corti¬
costeroid compared to patients receiving placebo. The benefit is relatively
small, however, and should be balanced against the potential for sideeffects associated with the use of methotrexate.
110S
Abstracts of Original
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Investigations, CHEST 1997.Poster Presentations
Tuesday, October 28, 1997
Issues in Asthma, continued
EFFECT OF SHORT-TERM EXPOSURE TO VAPORIZED IN¬
CENSE ON EXPIRATORY FLOW RATES OF ASTHMATICS
Badr R Al-Ghamdi, FRCPC, FCCP; Lo Nwoye, PhD.King Saud
University, College of Medicine, Abha, Saudi Arabia
Purpose: Oud is an incense commonly used at social gatherings in
Saudi Arabia. It emits a pleasant smell when vaporized and is frequently
inhaled. This study was performed to determine the effect of such
inhalation on expiratory flow rates in patients with bronchial asthma
(B.A.).
Methods: 27
Duration and
B.A. were individually exposed to Oud.
of exposure were similar to those which obtain at
patients with
manner
social gatherings. Spirometry was performed before, immediately after,
and 40 minutes after exposure. A control group of 23 normal volunteers
was similarly studied. Results for timed expiratory volume (FEVj, peak
and mid-maximal expiratory flow rate
expiratory flow rate (PEFR)Deterioration
(MMEF25.75) were analysed.
by 15% or more was consid¬
ered significant.
Results: Immediately after exposure, 12 B.A. patients (57%) showed
deterioration in MMEF25_75 as compared to only 3 subjects
significant
(13%) in the control group. This was statistically significant (P<0.05). A
similar statistically significant difference was observed in the proportions
of patients versus controls who showed significant deterioration of
MMEF25.75 40 minutes after exposure. However, no significant differ¬
ences were observed for FEVX and PEFR.
Conclusions: Short-term exposure to Oud can be considered as a
trigger for an early asthma response.
Chnical Implications: This is the first report to document that this
incense is a trigger for an early asthma response. Asthmatics
particular
should be informed to avoid exposure to Oud.
CORRELATION BETWEEN CLINICAL DIAGNOSIS AND
BRONCHOALVEOLAR LAVAGE IN ASSESSMENT OF ASTH¬
MATIC COMPONENT IN PATIENTS WITH CHRONIC OB¬
STRUCTIVE LUNG PULMONARY DISEASE (COPD)
Kumar Ashutosh, MD; RE Hutchison.VA Medical Center and SUNY
Health Science Center, Syracuse, NY, USA
To correlate a clinical diagnosis of asthmatic component in
Purpose:
with COPD with T-cell markers of asthma in fluid obtained by
patients
bronchoalveolar lavage (BAL).
Methods: T-cell subsets and CD4+/CD8+ T-cell ratio were analyzed
in BAL samples in 17 and 4 patients with COPD and 4 subjects with and
without COPD. Patients were divided clinically in two groups, those with
asthmatic component (A) and those without (C).
Results: Groups A and C included 9 and 8 patients respectively. CD4+
and CD3 were higher in A (0.272±0.189 and 0.408±0.257 respectively)
than in C (0.077±0.076 and 0.194±0.179; P<.05). Furthermore CD4/
CD8 ratio was higher in A than C (x2=7.91, P<.01).
Conclusions: Clinical diagnosis of asthmatic component in patients
with COPD is associated with cellular markers of asthma in BAL.
Chnical Implications: Chnical features in patients with COPD can be
used to diagnose presence of immunologic markers in BAL suggestive of
asthmatic component and could guide therapeutic considerations.
A DOUBLE-BLIND COMPARISON OF INHALED BE¬
CLOMETHASONE DIPROPIONATE AND TRIAMCINOLONE
ACETONIDE IN ASTHMA
Edwin Bronsky, MD1, P Korenblatt2, AG Harris*, R Chen*. *ScheringPlough
Corp Phase IV Research Unit, Kenilworth, N.J. 1Salt Lake City,
Utah. 2St. Louis, Missouri
Purpose: To compare beclomethasone
dipropionate MDI (BDP) 336
with triamcincolone acetonide MDI (TA) 800 meg/day in
meg/day with
The TA
asthma. BDP was administered without a
patients
spacer.
inhaler has a built-in, small-volume (113 mL) tube extender.
Methods: This 56-day, randomized, double-blind, double-dummy,
study was conducted at 16 centers in 329 patients with
placebo-controlled
mild to moderately severe asthma (FEVX 50% to 90% of predicted). FEVX
was the primary efficacy measure. Other efficacy measures were FEF25%.
75%, FVC, and morning and evening PEFR.
Results: At endpoint both active treatments were significantly superior
to
FEVX. Mean increases in FEV1 were significantly
placebo inBDPmean
versus TA (day 28). Differences between active treat¬
greater for
mean increases in FEF25%_75%. Pairwise
significant for PEFR
showed BDP to be significandy
morning
superior to placebo at weeks 3, 4, 6 and at endpoint. Pairwise differences
between the active treatments were significandy better for BDP at
endpoint for mean evening PEFR. BDP was significantly superior to TA
for FVC (days 28 and 56). Significantly fewer adverse events occurred
with BDP (8.2%) and TA (15.1%) than with placebo (22.3%; P=0.013).
The evidence of adverse events, including oropharyngeal events, was
similar in the two active treatment groups.
Conclusion: BDP MDI 336 meg/day is at least as effective, and similar
in safety, to TA MDI 800 meg/day, with its built-in tube extender.
Chnical Implications: Inhaled BDP and TA are safe and effective at
their recommended daily doses. BDP may provide a clinical advantage in
some efficacy measures. TA with its tube extender offers no clinical
advantage versusaBDP. from
Shering-Plough, Inc.
Supported by grant
ments were not
differences in
mean
UNCONTROLLED OXYGEN ADMINISTRATION AND CARBON
DIOXIDE RETENTION IN ASTHMA
Jason W Chien, MD; RA Ciufo, MD; ME Skowronski, RRT;
ER McFadden, Jr, MD.University Hospitals of
Cleveland, Cleveland, Ohio, USA
JA Nelson, CRTT;
Purpose: It is generally assumed that uncontrolled administration of
oxygen (Os) to acutely ill asthmatics is without hazard. It is possible that
individuals with severe obstruction may retain carbon dioxide (C02) when
100% 02. This study was undertaken to test this hypothesis.
given
Methods: Acutely ill asthmatics were recruited in the emergency
department. Arterial blood gases (ABG) were drawn and measurements of
one second forced expiratory volume (FEV1) were obtained before and
after the administration of 100% 02 for 20 minutes. Selected subjects
were restudied after their episode resolved.
Results: Data were collected on 27 volunteers. Pre-100% Oa FEVL
1.46±0.13 (SEM) L (53.3±4.4 percent predicted) and remained
averaged
constant throughout the study. The mean baseline ABG values were:
units; PaC02=35.6±l.l mmHG; PaO2=70.7±2.7 mm
pH=7.44±0.01100%
02, there was a linear inverse relationship between
Following
Hg.
the initial FEVX and the development of C02 retention (r=0.66;
p<0.0004). The lower the FEVl5 the greater the rise in PaC02. In patients
with an FEV1 <35% predicted, the PaC02 rose on average 4.4 mm Hg,
and in those subjects with a normal or high PaC02, frank respiratoiy
failure developed. In restudied patients, the effect of 02 administration
as the acute obstruction resolved.
disappeared
Conclusions: The administration of uncontrolled oxygen to acutely ill
asthmatics with severe airway obstruction may cause retention of C02 and
frank respiratory failure.
precipitate
Clinical Implications: This form of treatment is not innocuous, and
can no longer be recommended. It represents an unrecognized cause of
pulmonary insufficiency that may result in unnecessary admis¬
iatrogenic
sions to intensive care units and unwarranted ventilatory support.
INFLUENCE OF CONSTITUTIONAL AND ACQUIRED FAC¬
TORS ON BRONCHIAL HYPERRESPONSIVENESS IN ASTH¬
MATICS
MP Foschino Barbara, O Resta, S Talamo, G Pietrafesa, G Legari,
V Mastrosimone, V Laera.Respiratory Disease Chair, University of Bari,
Italy
Purpose: To evaluate the incidence of risk factors (atopy, sex, airway
infections and cigarette smoke) on bronchial hyperresponsiveness (BH)
we studied 500 asthmatics (188F, 312M) aged 16-65 years.
Method: All patients were submitted to clinical-anamnestic examina¬
tion, prick-test, Rast for common inhalant allergens and Bronchial
Provocation Methacoline Test (BPTm).
Results: Our results show an increased frequence of asthma in males
16-30 years, while females show a higher frequence of asthma in
aged
adult age (30-40), more high than males also aged 40-65 years correlated
to predominant role of sexual hormones in women. In our study the
subjects are prevalently non-smokers (78.85%) probably for natural
selection associated to asthmatic disease. The analysis of relation between
smoke and sex show a higher number of smokers among males aged 40-65
years, while females are smokers between 20-40 years. The correlation
among smoke, sex, respiratory infections doesn't show significant differ¬
ences among sexes. Respiratory infections appear to interest smokers,
CHEST/112/3/SEPTEMBER, 1997 SUPPLEMENT
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111S
Tuesday, October 28, 1997
Issues in Asthma, continued
demonstrating predisponent role of smoke as aggravating disease factor in
asthmatics. The 54.72% of our sample resulted atopies with higher
frequence
prevalently in males (68.38%). Females show a higher inci¬
dence of intrinsic asthma probably related to sexual hormones role and
vagal
hypertone. BH is more represented in atopies with intense response
to methacoline in perennial atopies. BPTm resulted positive in 56.30%
without significant differences between sexes, also if females seems to
have a more intense response in comparison to males.
Smokers showed an increased BH; atopies presented a correlation more
evident between smoke and BH showing intense response to methacoline.
Several studies demonstrated that asthma is acquired disease, while
genetic factors seem to be important determinants but not basic.
Conclusion: Our data confirm the role of constitutional and acquired
risk factors in the asthma pathogenesis.
Results: Both groups displayed a highly significant improvement in
starting at 1 hr & continuing even at 24 hrs. All asthmatics who
were earlier refractory to Beta2 agonists responded very well to steroid
therapy
irrespective of the delivery system used.
Conclusions: Corticosteroids improve the bronchodilator response of
Beta2 agonist in acute asthma, both immediately & after a prolonged
administration.
Clinical Implications: Steroids are mandatory in acute asthma partic¬
in subjects refractory to Beta2 agonists. Oral steroids are preferrable
ularly
to IV steroids as they are simple to administer & cheap, except in drowsy
SPRAY PLUME CHARACTERIZATION OF A NEW CFC-FREE
PROPELLANT METERED-DOSE INHALER
Brian J Gabrio; DJ Velasquez; RA McNally.3M, St. Paul, MN, USA
THE PREVALENCE OF ASTHMA, CHRONIC BRONCHITIS,
COPD, AND IMPAIRED LUNG FUNCTIONS IN ADULT POPU¬
LATION IN THE FINNISH LAPLAND
JLAKotaniemi*, A Sovijarvi0, M Nieminen***, B Lundback** and
Hos¬
Laitinen.*Lansi-Pohja Central Hospital, Finland; °University^Na¬
Helsinki, Finland; ***University Hospital, Tampere, Finland;
pital,
tional Institute for Working Life, Umea, Sweden
Purpose: The purpose was to determine and compare the spray
characteristics between albuterol metered-dose inhalers (MDIs) using
conventional chlorofluorocarbon (CFC) propellant and one formulated
with an alternative CFC-free propellant, HFA-134a. The characteristics
measured were maximum impact force, total spray momentum, spray
duration, and plume temperature.
Methods: A customized computer data acquisition system measured
and analyzed the dynamic spray characteristics as the MDI was fired at a
4.5 cm square plate that was 5 cm from the mouthpiece.
Results: The results show that CFC-propellant formulations produce a
force, larger total spray momentum and a lower
higher maximum impact
spray temperature than the CFC-free product (N 15 for force data and
N 10 for temperature data).
=
=
Max.
Impact
Force, mN
CFC/albuterol A
CFC/albuterol B
CFC-free/albuterol
CFC/albuterol A
CFC/albuterol B
CFC-free/albuterol
82.1±3.5
95.4±7.8
25.5±4.3
Momentum,
SpraymN
sec
.
6.4±0.1
6.9±0.2
2.2±0.3
Minimum Spray
Temperature, °C
Duration, msec
Spray
-25.7±9.4
-29.1±7.4
8.5±3.5
192.1±18.7
178.9±7.7
195.4±19.6
PEFR
subjects.
Purpose: The FlNEsS-study is an epidemiological respiratory survey in
FiNland, Estonia and Sweden. The aim is to assess the prevalence of
asthma, chronic bronchitis, respiratory symptoms, allergy, bronchial hy¬
perreactivity and impaired lung function values in the 20-69 years old
population.
Methods: In Finland the study is carried out in the southwest and
central Lapland and the city of Helsinki. Studies using the same methods
are done simultaneously in four other centers in Sweden and Estonia. The
whole population in the southwest and central Lapland is about 140,000
20-69 years of age. In November 1995 a
people, or them about 90,000 are
I) was sent to randomly chosen 8.005 persons
postal
questionnaire
(phase
in ages 20-69 years living in the study area, response rate was 85%. The
FinEsS questionnaire is based on IUATLD, BMRC and OLIN question¬
naires and contains questions about heredity, respiratory symptoms,
asthma, chronic bronchitis, symptoms in special circumstances, smoking
habits and profession. In the phase II randomly chosen 1230 responders
from the postal study are invited to clinical study which consists of
interviews and questionnaires, pulmonary function tests and bronchial
tests and PRICK-tests for type-1 allergy.
hyperreactivity
Results: Prevalences from postal study and 382 persons studied in the
phase II:
Current asthma
Symptomatic chronic bronchitis
COPD
Conclusions: The computerized data acquisition system is a useful tool
to investigate the dynamic characteristics of metered-dose inhaler sprays.
The CFC-free MDI produces a softer, warmer spray than that produced
the CFC formulations.
byChnical
Implications: This experimental apparatus simulates an MDI
spray striking the back of a patient's throat. Spray force and temperature
are relevant as they are the main determinants of the cold freon effect.
Supported by 3M Pharmaceuticals.
STEROIDS IN ACUTE ASTHMA: A COMPARISON OF TWO
DELIVERY SYSTEMS
U Gollapalli, R Ranjit, S Nabar, S Pednekar, S Tamane, A Paidhungat,
FCCP.Nair Hospital, Mumbai, India
Purpose: Bronchial asthma is an inflammatory condition & early
steroid administration becomes the mainstay of treatment. We compared
the effects of Oral & I.V. steroids in acute asthma.
Methods: Forty severe asthmatics (PEFR<100/min), not responding
to adequate bronchodilators (nebulised salbutamol & I.V. Aminophylline)
and who had not received steroids earlier participated in the study.
were excluded.
Subjects with complications or concomitant diseases
X (n=20) received oral
Subjects were categorised into two groups.
Group
prednisolone
(0.6mg/kg/day) Group Y (n=20) received IV Hydrocortisone
3 mg/kg bolus followed by a 24 hour infusion of 0.5 mg/kg/hr. Bronchodi¬
lators were continued in both the groups. Peak expiratory flow rate
(PEFR) was recorded at Vfe, 1, 3, 6, 12 & 24 hrs.
112S
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Airways obstruction
5.4%
8.9%
6.0%
28.9%
Conclusions: The prevalence for asthma, chronic bronchitis, COPD
and airways obstruction seems to be higher compared to former studies in
Finland. From the results can be estimated that the rate for undiagnostised sub-clinical asthma and COPD are both about 10% in adult
population in the Finnish Lapland.
GLUCOSE INTOLERANCE AMONG PATIENTS WITH ASTHMA
TREATED WITH HIGH DOSE OF INHALED CORTICOSTE¬
ROIDS
Hani Lababidi, MD; R Basir, MD; V Subramanian, MD; A Lalani, MD;
L Shapiro, MD; T McGarry, MD.Divisions of Pulmonary Medicine and
Endocrine, Lincoln Medical and Mental Health Center, New York
Medical College, The Bronx, NY
Purpose: High dose of inhaled corticosteroids (IC) are often given to
patients with severe asthma. The purpose of this study is to determine the
incidence of glucose intolerance in asthmatics receiving high dose of IC.
Methods: We measured fasting blood sugar (FBS) and Glycosylated
(GH) in severe asthmatics attending our clinic. Patients
hemoglobin
characteristics and dosages of IC were compared using student t-test and
Chi-square.
Abstracts of Original
Investigations, CHEST 1997.Poster Presentations
Tuesday, October 28, 1997
Issues in Asthma, continued
Results: Out of 99 patients with severe asthma, 28 (28%) were known
diabetics and were excluded from the study. Out of 71 patients tested, 33
(46%) were found to have either elevated FBS (>120 mg/dl) or high GH
(>7.5%) (Group I); while 38 (54%) had had normal FBS and GH (Group
II). The comparison of the 2 groups was as follows:
Group I
N
Age
Sex
F
M
Duration of Rx
Beclometh.
Triamcinol.
Flunisolide N
N
p.g/day
N
u,g/day
fig/day
FBS
GH
Group II
33
38
55.8±8.4
50.0±12.0
28
5
4.2±2.6
21
1012±407
6
2700 ±1144
6
3333±1033
111±27
8.85±1.90
30
8
3.6±2.2
27
943±279
7
1886±430
4
3250±957
P-value
0.034
0.556
0.651
0.681
0.553
0.778
0.132
0.497
0.879
90±10
6.60±0.56
Conclusion: 1) Glucose intolerance was detected in 46% of severe
asthmatics attending our clinic and receiving high dose IC. 2) No
differences were found among the 3 IC studied. 3) No dose
significant
effect relationship at the high dosages of IC used was observed. 4) GH was
elevated in 23 out of 33 patients (70%) with normal FBS.
Chnical Implication: Patients receiving high dose IC should be
periodically assessed for glucose intolerance by checking FBS and GH.
ASTHMA IN PENNSYLVANIA (PA): A STATEWIDE SURVEY OF
ALL SCHOOL NURSES
Alaa Al El-Gendy, MD; S Mangione, MD; D Tollerudd, MD.Allegheny
University of the Health Sciences, Philadelphia, PA
Purpose: Asthma is the most common chronic illness in childhood, and
the number one cause for hospitalization and prescribed therapy in this
age group. Although its prevalence among school-children can be as high
as 10%, well-designed population studies in the U.S. are limited.
Methods: To better analyze the impact of this disease on school
activities and school children, we designed a two-page fifty-item question¬
naire; aimed at surveying the reported prevalence of asthma, its impact on
absenteeism and academic performance, obstacles towards its successful
management, and possible solutions. We mailed this questionnaire to all
PA nurses of both public and non-public schools (N=5,300). Data were
between January and May 1997.
gathered
Results: 2037/5300 (38.4%) schools returned the questionnaire. Over¬
all, 6.4% of all children were known to school staffs as being asthmatic;
half of these were requiring daily asthma medications. Compared to the
rest of the state, Philadelphia and Pittsburgh had no significant difference
in reported asthma prevalence, but had a significantly lower percentage of
children requiring daily medications (45.5% vs 51.7%, P=.01). Large
cities had less full-time nurses (28.5% vs 38%, P=.02) and perceived
asthma as having worsened significantly more when compared to the rest
of the state (0.56 vs 0.38, on a -1
+ 1 scale, P=.001). Communication with families and identification of all
asthmatic children were considered essential for better asthma care
(5.5±.8 and 5.3±1, on a 1-6 scale)
Conclusions and Chnical Implications: This study suggests that the
and severity of "diagnosed and reported" asthma in Pennsyl¬
prevalence
vania school-children is similar to the national average. Our data, however,
do not include undiagnosed asthmatics and asthmatics not known to
school staff. Our figures may therefore underestimate the true prevalence
of this disease.
Supported by Merck Pharmaceuticals.
RELEASE OF CHEMOKINE REGULATED UPON ACTIVATION
IN NORMAL T CELLS EXPRESSED AND PRESUMABLY SE¬
CRETED (RANTES) FROM PLATELETS IN ASTHMATIC PA¬
TIENTS
Chie Moritani, MD; Y Haruta, MD; S Ishioka, MD; M Kambe, MD;
M Yamakido, MD.The Second Department of Internal Medicine and
of Clinical Laboratory Medicine, Hiroshima University
Department
School of Medicine, Hiroshima, Japan
Purpose: Platelets contain some chemokines, such as platelet factor 4
and RANTES, which are capable of inducing or augmenting allergic
inflammatory
responses. We investigated whether platelets were activated
in asthmatics with increased release of the preformed chemokines. In
addition, we also investigated the influence of oral administration of
on them.
theophylline
Methods: Twenty-five normal volunteers, 19 asthmatics taking no oral
with asthma treatment (group A), and 18 asthmatics
drugs associated
taking oral theophylline
(group B) were evaluated. We measured CD62P
expression on platelets using flow cytometry and RANTES level in
buffer supernatants using ELISA kit.
platelet-rich
Results: While both the CD62P expressions and RANTES levels
without stimulation were similar among the three groups, those after
stimulation by agonist, such as thrombin, PAF, or STA2, in group A were
higher than those in the normal subjects, and using STA2 the difference
was statistically significant (p<0.05). In contrast, in group B, both the
CD62P expressions and RANTES levels after stimulation by each agonist
were significantly lower than the corresponding levels in group A
(p<0.05).
Conclusion and Chnical Implications: We conclude that agonistmediated activation of platelets is augmented in asthmatics resulting in
enhanced release of chemokine such as RANTES, which could be
administration of theophylline.
suppressed by oral
research grants from the Japanese Ministry of Education,
Supported
by
Science, and Culture.
VIP HYDROLYSIS IS INCREASED IN THE PREGNANT PA¬
TIENT WITH ASTHMA
O Olopade, MD; J Yu, MD; J Abubaker, MD; T Myles, MD;
Christopher
I Rubinstein, MD; S Paul, PhD.University of Illinois, Chicago, Illinois
University of Nebraska Medical Center, Omaha, Nebraska
Purpose: Vasoactive intestinal peptide (VIP) is a neuropeptide bron¬
chodilator and is thought to be involved in non-adrenergic non-cholinergic
bronchial smooth muscle relaxation. Depletion of VIP in airway nerves of
patients dying from asthma has been demonstrated. We have previously
shown that hydrolysis of VIP by circulating catalytic VIP antibodies is
increased in asthma in comparison to controls. The purpose of this study
to
of
and
determine the effects pregnancy and asthma on VIP hydrolysis
by circulating
catalytic VIP antibodies, because pregnancy is known to
immune responses.
modify
Methods: We determined VIP hydrolysis in 17 women in the third
with and without asthma:
trimester of
was
pregnancy
pregnant, asthma; n=9;
pregnant, non-asthma; n=8 and 16 non-pregnant women with and
without asthma: non-pregnant asthma; n=9; non-pregnant, non-asthma;
n=7.
Results:
Patient
Population
Non-pregnant, non-asthma, n=7
Non-pregnant asthma, n=9
Pregnant non-asthma, n=8
Pregnant asthma, n=9
Data
are
Age>
VIP
34.4±2
32.0±3
25.9±2
25.2±2
1.98±0.9
5.39±0.8*
5.17±0.4
7.48±1.2f
mean±SEM.
non-asthma;
*=p<0.05 inin comparison toto non-pregnant,
comparison pregnant, non-asthma. Substrate concentra¬
t=p<0.05
tion, 110 pM.
Conclusion: Pregnancy and asthma are independently associated with
increased levels of VIP hydrolyzing antibodies.
CHEST / 112 / 3 / SEPTEMBER, 1997 SUPPLEMENT
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cleaved,
pM/6h
yr
113S
Tuesday, October 28, 1997
Issues in Asthma, continued
SALMETEROL IN ACUTE ASTHMA: DO ONGOING STEROIDS
HELP?
Pednekar, S Drago, U Gollapalli, S Tamane, V Iyengar, S Nabar,
Pai-dhungat.Nair Hospital, Numbai, India
Purpose: Salmeterol, a long-acting B2 agonist, is important in therapy
of nocturnal asthma. Steroids are anti-inflammatory & upregulate B2
receptors & play a vital role in acute asthma. We observed the effects of
steroids on the immediate & long term response to inhaled
ongoing
salmeterol.
Methods: Sixty-one young subjects with acute asthma were selected for
the study after excluding concomitant diseases. Details of ongoing therapy
were noted & tests were done after omitting bronchodilators for a day.
Pulmonary function tests (PFT) were recorded before & serially up to 6
hrs. after administering salmeterol (50 (xg) by metered-dose inhaler
(MDI) with a spacer device. They were then advised to take 2 puffs of
salmeterol BID with a 50% reduction in existing drugs & were evaluated
after 4 weeks.
S
A
Results: Salmeterol action lasted from Vz hr to 6 hrs., the best effect
being on small airways.
Subjects on ongoing steroids (n=26) showed a
greater response than those without steroids (n=35). Thirty eight subjects
completed the trial. Those who were on steroids (n=20) had a greater rise
in basal PFT & better control of nocturnal asthma at the end of 4 weeks
than those not on steroids (n=18) (74% vs. 56% rise).
Conclusion: Salmeterol is an excellent drug for acute asthma with
immediate & long term bronchodilatation which is enhanced by ongoing
steroids.
Chnical Inclinations: Salmeterol should be regularly combined with
steroids.
Supported by CIPLA Pharmaceuticals.
BRONCHIAL HYPERREACTIVITY AND GASTROESOPHAGEAL
REFLUX (GER): A MORE SENSITIVE PARAMETER FOR DE¬
TECTING THE EXTENT OF ACID EXPOSURE
*C Pomari, °M Dinelli, °S Passaretti; *C Micheletto; *R Dal Negro
*Lung
Dept., Bussolengo Gen. Osp, Verona & °Gastroenterologic Unit, S.
Raffaele Osp., Milano Univ, Italy
of pH<4" (%RT) represents the
Purpose: At present, "total reflux time
on the esophageal acid exposure,
quantitative indicator which informs
even though it is widely variable in adults1: a new indicator was calculated
("Area under pH4"-AU4)2, being 4% for %RT and 37 pHxmin for AU4
their normality cut-offs. Purpose of the study was to assess and compare
the sensitivity of both %RT and AU4 in discriminating the hyperreactive
response to methacholine (MCh).
Methods: %RT and AU4 were calculated in 27 non-smoker, non-atopic
with persistent cough and GER (22 f.; 36.6 yr±1.6 s.e., basal
subjects,
FEV1 105.8% pred.±2.9 s.e.), differently responder to MCh. After
=
EFFECT OF SALMETEROL TREATMENT ON DIURNAL PAT¬
TERN OF BRONCHODILATOR RESPONSES IN ASTHMATICS
Tung-Heng Wang, MD*, GB Marks, MD**, C Salome, BS**,
MD**.Chest Division, Department of Internal Medicine,
AJ Woolcock,Medical
Kaohsiung of CollegeThe
Hospital, Kaohsiung, Taiwan ROC, and
**Department Medicine, University of Sydney, Sydney, Australia
Purpose: To assess the effect of salmeterol (Salm) on diurnal responses
of airway caliber to short-acting salbutamol (Salbu) in asthmatics.
Methods: Nine patients with asthma were assigned, in random order,
to each of four treatment regimens: control for at least three weeks (No
Salm tx), 100 jutg for 1 day (Salm 100S), 50 |xg for 4 weeks (Salm 50L), and
100 jxg for 4 weeks (Salm 100L). Salmeterol was administered at 8 am and
9 pm each treatment day. On the last day of each treatment period,
change of FEV: (AFEVl5 which equals FEV: post Salbu minus FEVl
before Salbu) in response to Salbu 200 (xg was measured at 4 pm, 9 pm,
and 6 am in the following morning.
Results: Without salmeterol treatment (No Salm tx), AFEVX at 6 am
(0.48±0.11 I, mean±95% CI.) was greater than that at 4 pm (0.30±0.12
I, p=0.024) and that at 9 pm (0.30±0.11 I, p=0.041). There was no
difference in bronchodilator responses among clock hours with
significant
the 3 salmeterol regimens. Values of AFEVjl (mean±95% CI.) with
salmeterol treatment are listed below.
AFEV19 I
4pm
9pm
6
am
Salm 100S
Salm 50L
Salm 100L
0.11±0.08c
0.11±0.05a
0.17±0.06a
0.07±0.03c
0.12±0.06b
0.13±0.07d
0.08±0.04b
0.11±0.08d
0.15±0.05d
ap<0.05, bp<0.025,
cp<0.01, dp<0.001 in comparison with correspond¬
ing AFEVX at the same clock hour of No Salm tx.
Conclusions: Salmeterol treatment reduced the magnitude of, and
the diurnal pattern of bronchodilator responses in asthmatics.
changed
Chnical Implications: Asthmatics treated with salmeterol may reduce
the need of rescue short-acting bronchodilator.
T-H Wang was funded by Department of Social Education, Ministry of
Taiwan ROC.
Education, Executive
Yuan,
Issues in Cancer of the Chest:
Chemotherapy
Surgery &
VINORELBINE, CISPLATIN (HIGH DOSAGE)
AS INITIAL
TREATMENT FOR PREVIOUSLY UNTREATED NSCLC STAGE
IIIB: PRELIMINARY RESULTS AND SURGICAL CONSIDER¬
ATIONS
A Maiorino2, S Cigolari1, M Massimo2, C Curcio3, R Sessa2, &
T Vasta3.1Universita Federico II, Medicina III (Napoli, Italy). 2Hospital
Monaldi, Surgery I and II (Napoli, Italy). 3Hospital Ascalesi, Surgery
informed consent, a 24 h pH-monitoring was performed (by acombined
monocristant antimony catheter and a proximal sensor to locate the LES,
connected to a recorder Digi-trapper MKIII-Synectics Med, Stockholm,
Sweden). In different days, patients inhaled doubling MCh concentrations
(50-3150 meg) through a dosimeter (Mefar MB3, Brescia, Italy), up to the
provocation dose (PD20 FEVJ.
Results: Patients were divided into 3 groups: A) 9 subjects with normal
%RT and AU4 values (2.1%±0.1 s.e. and 29.9 pHXmin±4.4 s.e.,
9 subjects with normal %RT (2.2%±0.3 s.e.) and
respectively);AU4B) (48.8
pathological
pHXmin±2.3 s.e.); C) 9 subjects with pathological
%RT (11.01%±2.4 s.e.) and pathological AU4 (402.3 pHXmin± 125.4
s.e.). PD20 FEV-l were: 1167 mcg±272.3 s.e. in group A; 208.8 mcg±76.3
s.e. in group B; and 133.5 mcg±37.2 s.e. in group C, respectively.
Significant bronchial responses to MCh was assessed only in group B and
C, which both proved different from group A (Kruskal-Wallis test;
p<0.001).
Subjects of group B proved different from those of group C
in terms of AU4 mean value (p<0.02), being both different from
only
normal subjects in group A (p<0.001).
Conclusions: 1) In adults, AU4, but not %RT, proves related to the
extent of bronchial response to MCh; 2) the relationship with the extent
of the esophageal acid exposure seems particularly strict; 3) AU4 proves
suitable in discriminating those subsets of GER patients where the
pathological
response to MCh would otherwise remain unexplained.
Dis. Sci., 1988;33:1127-33
xDig.Pediatr.
Gastroenterol. Nutr., 1989;9:934-9
2J.
(Napoli, Italy)
The combination of vinorelbine (VNR) and cis-platin has
Background:
been shown to be active in recurrent and/or metastatic NSCLC
previously
Stage IIIB. (Le Chevalier, JCO 1994). This pilot study was carried out
with the aim of evaluating the effectiveness of this combination in patients
with previously untreated, locally advanced NSCLC (Stage IIIB).
Methods: 30 pts ^75 years old, between April 1996 and November
1996, were accrued: 28 ofthem were evaluable (1 too early, 1 lost to follow
median PSI; median age 61 Y (38-75Y).
up):Treatment:
NVB 30 mg/m2 on DI and D8+CIS-PLATIN 120 mg/m2
on DI in a 21 days schedule for 3 cycles before restaging; GM-CSF was
in case of severe neutropenia.
permitted
Results: Aften 3 cycles we had 57% of PR (16/28): 8 of them were
resected; all responders were confirmed by an independent external
expert group: 6/28 no change and 6/28 progressive disease. In the 8 pts
resected we had a down staging of neoplasia: in 3 pts the pN was No.
Conclusions: The NVB+CIS-PLATIN (High dosage) as neoadjuvant
scheme showed a high RR (57%): good is the resectability: the autors will
focus the attention on the toxicity general and local (particularly for pts
114S
Abstracts of Original
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Investigations, CHEST 1997.Poster Presentations