I have been working on the twitch pressure of mouth,
diaphragmatic and tracheal (airway) for several years
and had done the work about the relationship between
the twitch pressure of mouth or the twitch pressure
of tracheal and twitch pressure of diaphragmatic in
ventilated patients because of respiratory failure or
during general anaesthesia because of abdomen
operation. Recently, when I read of t...
I have been working on the twitch pressure of mouth,
diaphragmatic and tracheal (airway) for several years
and had done the work about the relationship between
the twitch pressure of mouth or the twitch pressure
of tracheal and twitch pressure of diaphragmatic in
ventilated patients because of respiratory failure or
during general anaesthesia because of abdomen
operation. Recently, when I read of the article
'Can diaphragmatic contractility be assessed by
airway twitch pressure in mechanically ventilated
patients?' (Thorax 2003;58;58-62), I found that I
had some different ideals from the writers.
First, of the 133 twitches recorded in our
patients, 37 were discarded for the following
reasons: cardiogenic changes in oesophageal pressure
(n=4); my ideal is that cardiogenic changes in
oesophageal pressure is always present and the twitch
pressure was different when the stimulation was given
during different cardiac cycle. The measurement of
oesophageal pressure was effected by cardiac cycle and
the effect was larger in lying position than in
sitting position. The negative pressure of thoracic
cavity did not affected the effect of cardiac cycle
on the oesophageal pressure. The function of diaphragm
was overestimated by the twitch oesophageal pressure
measured during systole phrase, but underestimated by
that during diostolic phrase and the effect of
cardiac cycle on the oesophageal pressure could be
eliminated by mathematical filter.
In one of my studies,
25 patients were involved. The dynamical
oesophageal pressure were measured in the sitting
position, the supine positions before and during
general anaesthesia and twitch oesophageal pressure
were measured in the supine positions before general
anaesthesia. The changing value of dynamical
oesophageal pressure in the sitting position, the
supine positions before and during general anaesthesia
was respectively (1.6±1.1)cmH2O(2.7±1.2)cmH2O and (2.3±1.2)cmH2O and there was a significant
difference between sitting position and the supine
position before general anaesthesia (P<_0.01 or="or" during="during" general="general" anaesthesia="anaesthesia" p0.05="p0.05" while="while" there="there" was="was" not="not" different="different" between="between" the="the" supine="supine" positions="positions" before="before" and="and" p="p"/>0.05).
The twitch
oesophageal pressure during systole and diostolic
phrase were respectively (16.3±6.6) cmH2O and (14.1±6.1) cmH2O and there was a significant differentiation
(P=0.000) and a relationship (r=0.920, P=0.000)
between them, but after eliminated by mathematical
filter, they were respectively (15.2±6.2)cmH2O and (15.0±6.0)cmH2O (P>0.05) and had not a differentiation each other (P>0.05).
The mathematical
filter method was shown below:
Second, the reason that Paw tw was more negative than
Poes tw in 10 of 13 patients was that the compression
of the oesophagus and balloon by the heart could,
from a functional stand point, increase the elastance
of the anatomical structures surrounding the balloon,
and the increased elastance of these structures would
dampen the transmission of intrathoracic pressure to
the lumen of the oesophagus. However, my opinion was
that the basic pressure before twitch was the key
point. Before twitch the tracheal pressure was 0, and
the oesophageal pressure was negative. However, after
twitch stimulation, the end point of pressure was
almost the same, As a result, the Paw tw was more
negative than Poes tw.
Third, patient 6 had the total PEEP, airway pressure
and oesophageal pressure was respectively 6.1, ¨C2.8
and ¨C3.6 cmH2O. The PEEP was higher, before twitch
stimulation, the abdominal muscle may contracted and
reduced the oesophageal and tracheal pressure,
especially the later. In my opinion, in these
respiratory patients, the twitch pressure should be
measured under sedation to make exact the result.
I hope future discussion.
I would like to share my views again after hearing from you that what clinical criteria and biochemical parameters for the remission in asthma have been used in your study.
What partameters were compared for the asthma remission in spirometery values pre and post remission phases.
In the complete clinical remission what predictors have been taken into consideration for the remission. No doubt remi...
I would like to share my views again after hearing from you that what clinical criteria and biochemical parameters for the remission in asthma have been used in your study.
What partameters were compared for the asthma remission in spirometery values pre and post remission phases.
In the complete clinical remission what predictors have been taken into consideration for the remission. No doubt remissions do occur but what should be the definitive clinical, biochemical and spirometric parameters that can be considered in future if an asthmatic is to remit.
I would be obliged to get educated on this interesting subject from a learned and experienced researcher S Guerra.
Thankin you
Dr.Anil Bhatia
Senior consultant physician.(visiting)
apollo hospital.
delhi rangappu@hotmail.com
It is generally appreciated that the practice of stepping-down inhaled corticosteroid (ICS) therapy in patients with stable asthma is poorly implemented, albeit in the background of limited evidence.1 Indeed, the appreciation for stepping-down ICS therapy once asthma control is attained is well established within the Global Initiative for Asthma (GINA) guidelines2 and has recently been...
It is generally appreciated that the practice of stepping-down inhaled corticosteroid (ICS) therapy in patients with stable asthma is poorly implemented, albeit in the background of limited evidence.1 Indeed, the appreciation for stepping-down ICS therapy once asthma control is attained is well established within the Global Initiative for Asthma (GINA) guidelines2 and has recently been adopted by the British Thoracic Society (BTS) and Scottish Intercollegiate Guidelines Network (SIGN) consortium.1
In the latter guidelines, it is recommended that a 25 – 50% of reduction in ICS dose be implemented at 3-monthly intervals.1 A large study in primary care has shown that patients with stable asthma on moderately high doses of ICS can be safely stepped-down without compromising asthma control.3 However, there are currently no data evaluating the practice of stepping-down ICS therapy in patients with stable asthma in secondary care. Despite transforming the management of asthma, ICS therapy exposes an individual to both local and systemic adverse effects.4 Indeed, when taken at high doses, the ICS dose-response curve for systemic adverse effects becomes steep, with little further therapeutic gain.5,6 Furthermore, the addition of second-line controller therapy may be more advantageous than merely increasing the ICS dose alone.7
We carried out a retrospective study to establish whether asthmatic patients attending a respiratory clinic in secondary care were being advised to reduce their ICS dose following a period of stability.
Methods
We assessed patients with asthma being followed-up in the respiratory clinic and retrospectively analysed data for the preceding 12-month period. Strict exclusion criteria were applied. Patients who were actively receiving or had received either oral or parenteral corticosteroids, or immunosuppressive therapy during the 12-month period were not considered eligible for inclusion. Patients also had to be exacerbation-free during this period. Classification of asthma severity was based on GINA guidelines.2
Results
Sixty consecutive patients with asthma were assessed in clinic. 2 patients were receiving parenteral corticosteroids, 4 patients were receiving immunosuppressant therapy, 14 patients were receiving oral corticosteroids, and 28 patients had an asthma exacerbation during the preceding 12 months. Therefore, using strict exclusion criteria, 12 patients were included in the data analysis.
Patient demographic data are shown in Table 1. 3 men and 9 women with mean ± standard error of mean age of 56 ± 6 years and forced expiratory volume in 1 second
(FEV1) of 1.97 ± 0.26 l (73 ± 6 % predicted) completed the study. The mean BDP equivalent ICS daily dose was 1267 ± 140 µg and patients had either moderate (n = 6) or severe (n = 6) asthma. 2 out of 12 patients had step-down in ICS therapy where one patient (number 10) had a 33% reduction in ICS dose from an initial daily dose of BDP 1500µg, having had stable asthma for 11 months, while the other patient (number 11) had a 50% reduction in ICS dose from an initial daily dose of fluticasone propionate (FP) 1000µg, having had stable asthma for 8 months. The remaining 10 out of 12 patients continued on the same dose of ICS despite having had stable asthma during the preceding 12 months. There were no significant differences in any outcomes comparing patients with and without step-down in ICS therapy.
This is the first study to demonstrate that stepping-down ICS therapy in patients with stable asthma is not being routinely adopted in secondary care. Most of the patients were maintained on their usual dose of ICS irrespective of the fact that their asthma had been clinically stable during the preceding 12 months. It is noteworthy that no deterioration in asthma control occurred in the two patients who had step-down in ICS therapy.
We appreciate that our cohort of patients were small in numbers. This was simply a reflection of the difficulty in recruiting patients for such a study in secondary care. Asthma is a chronic condition that is mainly managed in primary care. Indeed, patients who are referred for specialist input, consist primarily of difficult-to-control asthmatics or those who pose diagnostic uncertainties. Therefore, patients with asthma are seldom followed-up in secondary care, especially when diagnosis has been established and treatment commenced. Furthermore, many patients being actively followed-up in secondary care consist of severe asthmatics requiring oral or parenteral corticosteroids, with some requiring immunosuppressant therapy. Such patients were excluded from our study due to the strict criteria that was employed. The requirement for patients not to have an exacerbation or a course of corticosteroids during the preceding 12 months further reduced our number of suitable patients. Therefore, we acknowledge that the population of asthmatics in secondary care may not reflect the true asthmatic population as a whole when compared to those seen in primary care. Nevertheless, these asthmatics do fulfill the criteria for step-down in ICS therapy and there was indeed no reason to treat them any differently in keeping with current guidelines.
A possible reason for the lack of the adoption of stepping-down ICS therapy in secondary care could be attributable to the relatively selective asthmatic population served by secondary care physicians, where most patients have severe, brittle or difficult-to-control asthma. When such patients are using appropriate pharmacotherapy and clinically stable, there is understandably a disinclination to titrate therapy downwards, in case one offsets the control of asthma, which has been difficult to attain in the first instance. Another reason for the less-than-ideal implementation of stepping-down ICS therapy may be attributable to the fairly recent adoption and recommendation of such an approach in asthma management by the BTS and SIGN consortium, owing in part to the substantial lack of available data on this issue.
The rationale behind recommending stepping-down ICS therapy once asthma control is achieved is indisputable. ICS has the propensity to be absorbed from the lungs and gastrointestinal tract into the systemic circulation, leading to adverse effects in a variety of body systems.4 Additionally, studies have shown that most of the therapeutic benefit of ICS can be achieved at fairly low doses; 100 – 250µg daily for FP5 and 400µg daily for budesonide.6 Moreover, the validity of high dose ICS therapy has been put into question in light of recent data showing that stepping-up therapy by doubling the dose of ICS may be ineffective in influencing asthma exacerbations.8,9 With the increasing popularity of combination ICS and long-acting ß2-agonist inhalers (67% of our patient cohort), stepping-down is more complicated as it is more difficult to reduce the ICS dose without first splitting the combination inhaler into its separate moieties.
In conclusion, secondary care physicians need to have a heightened awareness in terms of stepping-down ICS therapy in patients with stable asthma. Failing to do so may expose patients to unnecessary and prolonged treatment with high doses of ICS with potentially serious long-term adverse sequelae. Stepping-down ICS therapy not only reflects good practice but is also in accordance with current asthma guidelines.
References
BTS/SIGN. The British Thoracic Society and Scottish Intercollegiate Guidelines Network 2004 update to the British guideline on the management of asthma. Available at: http://www.brit-thoracic.org.uk/docs/asthmafull.pdf.
GINA. The National Heart, Lung, and Blood Institute and World Health Organisation 2004 update to the Global Initiative for Asthma guideline on the global strategy for asthma management and prevention. Available at: http://www.brit-thoracic.org.uk/docs/asthmafull.pdf.
Hawkins G, McMahon AD, Twaddle S, et al. Stepping down inhaled corticosteroids in asthma: randomised controlled trial. BMJ 2003;326:1115-20.
Lipworth BJ, Jackson CM. Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf 2000;23:11-33.
Holt S, Suder A, Weatherall M, et al. Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis. BMJ 2001;323:253-6.
Masoli M, Holt S, Weatherall M, et al. Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis. Eur Respir J 2004;23:552-8.
Shrewsbury S, Pyke S, Britton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 2000;320:1368-73.
Harrison TW, Oborne J, Newton S, et al. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet 2004;363:271-5.
FitzGerald JM, Becker A, Sears MR, et al. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations. Thorax 2004;59:550-6.
The authors of the UK guidelines on asthma have asked for feedback
based on audit.[1] The latest British guidelines for asthma management
suggest that children with moderate exacerbation of asthma presenting to
the accident and emergency unit (annexure 5) must be treated with beta
agonists: 2 to 10 puffs via a spacer and re-assed after 15 minutes. This
recommendation seems to be observed often in the...
The authors of the UK guidelines on asthma have asked for feedback
based on audit.[1] The latest British guidelines for asthma management
suggest that children with moderate exacerbation of asthma presenting to
the accident and emergency unit (annexure 5) must be treated with beta
agonists: 2 to 10 puffs via a spacer and re-assed after 15 minutes. This
recommendation seems to be observed often in the breach. We report our
experience in a UK university hospital with that component of asthma care
in the local guidelines
We did this retrospective audit of all children with exacerbation of
asthma who presented to A&E at the West Middlesex University Hospital,
between 1/11/04 and 9/1/05. Protocol mandated a prior diagnosis of
asthma. 87 children fulfilled the above criteria for inclusion in the
study. 90% of them had moderate exacerbation of asthma according to the
guideline criteria.[1] Among the 78 children with moderate exacerbation,
90% received nebulised salbutamol rather than beta-agonist via a spacer as
first line treatment.
We can only speculate why the protocol to first try a spacer in the
A&E is not followed. All the children studied here had previously been
diagnosed as asthmatic and so most of them would have beta-agonist and
spacer at home and would have tried this before presenting to the A&E.
Thus there may have been subtle or explicit pressure to scale up treatment
rather than give a further trial to a form of therapy that was tried at
home without success. A previous study has shown that lack of ‘outcome
expectancy’ was a major reason for non-adherence to asthma guidelines.[2]
The guidelines on asthma have been revised previously and the
recommendation of the use of pulsus paradoxus, to determine severity of
asthma, has been rescinded for ‘pragmatic reasons’ in the latest version.
The recommendation to use a spacer in the A&E may also need to be
reconsidered if the findings in our hospital are a reflection of more
widespread practice nationwide. We hope to use your correspondence column
and the electronic responses facility to gauge how widespread this problem
with guideline compliance is.
1. British Thoracic Society, Scottish Intercollegiate Guidelines
Network (SIGN). British guideline on the management of asthma. Thorax
2003;58(suppl)i 1-94.
We read with interest your approved guidance on the key issues which
should be considered in preparing a genetic association studies to become
acceptable for publication in Thorax [1-2]. While we agree with several
points in this guidance, there are still several other points that we see
as exaggerated or at best controversial.
We even can see that in the eight
genetic association studies p...
We read with interest your approved guidance on the key issues which
should be considered in preparing a genetic association studies to become
acceptable for publication in Thorax [1-2]. While we agree with several
points in this guidance, there are still several other points that we see
as exaggerated or at best controversial.
We even can see that in the eight
genetic association studies published in Thorax since 2004, at least some
of them do not conform to this guidance from points of population size,
number of polymorphisms studied and their functionality.
We can see this
clearly in the latest published association study by Yarden and colleagues
[3] who examined 4 polymorphisms in TNFalfa gene in cystic fibrosis
patients. Three of the studied polymorphisms were without functional
information, no assessment of linkage disequilibrium, haplotype analysis
or correction for multiple comparisons had been performed and the
population size; even after pooling the two different ethnic groups,
showed that the study was underpowered.
Regarding the population size required in your guidance, the numbers
appearing in table 1 are too high (regardless for the typing error that
caused the “Cases required” for “Minor allele frequencies” of 0.2 and
0.4 to be reversed). The reason for that is the unusual setting of the
power into 90% instead of the widely applied 80%. In fact, 80% power is
the default for the online genetic power calculator you yourself provided
in your editorial. Using that default of 80%, much lower numbers of cases
could be obtained and considered as having enough power e.g. with the
relative risk set to 2, only 130 or 170 cases are required when the
“Minor allele frequency” is 0.4 and 0.2, respectively. Accordingly, we
think that your assumption that (a study of 150 asthmatics and 150
controls is unlikely to be adequately powered) needs some modification
like adding to it (if the minor allele frequency is less than 0.3, or so).
Then regarding the functionality of a polymorphism, we agree that
studying known functional polymorphisms rather than random polymorphisms
in the gene of interest is advantageous in terms of detecting true disease
-associated variants. However, restricting the genetic association studies
to functional polymorphisms may lead to important polymorphisms being
missed. This is because many polymorphisms are difficult to assess their
functional effect either due to technical problems (e.g. intronic, coding-
synonymous or polymorphisms that are far up-stream or down-stream from the
studied gene) or due to absence of the full knowledge of the gene function
and how it might be influenced by the polymorphism.
Then regarding the population stratification, there is no doubt that
study population that contain ethnically or geographically unmatched
subjects may lead to spurious results and we do not think any researcher
would undertake an association study based on such a population anyway.
However, your assumption that even apparently homogenous population may
show sub-stratification and accordingly your request to have the study
populations typed for unlinked markers in order to identify any
stratification is lacking concrete scientific evidence. In fact, the
reference you cited [4] in addition to several other studies [5-7] have
indicated that there are few actual examples to support this assumption
and that there is growing recognition that population stratification might
not have been as important a problem as originally believed, and has
probably been a minor or even irrelevant factor for most non-replicated
association studies.
On the other hand, an important criterion in the evaluation of
genetic association studies was absent in your guidance, that is Hardy-
Weinberg equilibrium. Hardy-Weinberg disequilibrium in the control
subjects could result from genotyping errors, inbreeding, genetic drift,
mutation, or population stratification.
In conclusion, we agree with you on the importance of proper
selection of patients and controls, accurate definition of disease
phenotype, considering linkage disequilibrium and haplotypes, correction
for multiple comparisons and the need for a power calculation and
functional assessment of polymorphisms especially if they showed
association to the disease. Nevertheless, we disagree to disqualify any
study for its limited population size if it is still able to show
acceptable power, for its inability to check the functionality of the
studied polymorphisms or for its failure to genotype the whole population
for unlinked markers to exclude population stratification especially if
the genotype frequencies of the polymorphisms under study were within the
Hardy-Weinberg equilibrium.
References
1. Wedzicha JA, Hall IP. Publishing genetic association studies in
Thorax. Thorax 2005; 60: 357.
2. Hall IP, Blakey JD. Genetic association studies in Thorax. Thorax
2005; 60: 357-9.
3. Yarden J, Radojkovic D, De Boeck K, Macek M Jr, Zemkova D, Vavrova
V, Vlietinck R, Cassiman JJ, Cuppens H. Association of tumour necrosis
factor alpha variants with the CF pulmonary phenotype. Thorax 2005; 60:
320-5.
4. Cardon LR, Palmer LJ. Population stratification and spurious
allelic association.
Lancet 2003; 361: 598-604.
5. Wang Y, Localio R, Rebbeck TR. Evaluating bias due to population
stratification in case-control association studies of admixed populations.
Genet Epidemiol 2004; 27: 14-20.
6. Cardon LR, Bell JI. Association study designs for complex
diseases. Nat Rev Genet 2001; 2: 91-9.
7. Wacholder S, Rothman N, Caporaso N. Population stratification in
epidemiologic studies of common genetic variants and cancer:
quantification of bias. J Natl Cancer Inst 2000; 92: 1151-8.
The combination of acute and chronic haemondynamic effects in
obstructive sleep apnea have been associated with increased risk of
myocardial infarction, cerebrovascular accidents, hypertension, and
congestive heart failure. It is necessary to provide appropriate treatment
for Obstructive sleep apnea syndrome (OSAS).
Most health care providers offer nasal continuous positive airway
pressure...
The combination of acute and chronic haemondynamic effects in
obstructive sleep apnea have been associated with increased risk of
myocardial infarction, cerebrovascular accidents, hypertension, and
congestive heart failure. It is necessary to provide appropriate treatment
for Obstructive sleep apnea syndrome (OSAS).
Most health care providers offer nasal continuous positive airway
pressure (CPAP) or oropharyngeal surgery for these patients, but neither
approach has proved to be a panacea. Although the use of nasal CPAP after
pressure titration in the sleep laboratory offers effective reversal of
the obstructive apneas, the short- and long-term compliance becomes an
issue in more than 50% of patients.[1] Because it is relatively
noninvasive, most practitioners offer CPAP as the first line of treatment.
Oropharyngeal surgery is a commonly performed alternative to nasal CPAP
for OSAS.
The most important issue to surface with positive airway pressure
therapy has been that of patient compliance. This was objectively shown by
Kribbs and colleagues using pressure-sensitive hour meters in CPAP units.
They found that CPAP was actually used by only 46% of patients for greater
than 4 hours of sleep for 70% or more of nights.[2]
Weaver et al reported that the long-term pattern of compliance was
determined within the first week of usage and implies that the earliest
experiences with CPAP may be fundamental to compliance.[3]
Proper mask fit, appropriate pressure titration, and immediate
intervention to correct patient discomfort may be the most important
interventions to improving patient compliance.[4]
Sincerely
Dr. Murat Enoz
References
1- T. Young, P.E. Peppard, D.J. Gottieb, Epidemology of obstructive
sleep apnea: a population health perspective, Am. J. Respir. Crit. Care
Med. 165 (2002) 1217-1239.
2- Kribbs NB, Pack AI, Kline LR, et al: Objective measurement of
patterns of nasal CPAP use by patients with obstructive sleep apnea.Am Rev
Respir Dis 147:887-895, 1993.
3- Weaver TE, Kribbs NB, Pack AI, et al: Night-to-night variability
in CPAP use over the first three months of treatment. Sleep 20:278-283,
1997.
4- Millman RP, Rosenberg CL, Kramer NR: Oral appliances in the
treatment of snoring and sleep apnea. Clin Chest Med 19:69-75, 1998.
Obstructive sleep apnea is an increasingly well recognized disease
characterized by periodic collapse of the upper airway during sleep.
Obstructive sleep apnea (OSA) is characterized by periodic complete or
partial upper airway obstruction during sleep, causing intermittent
cessations of breathing or reductions in airflow despite ongoing
respiratory effort. It’s defined by the presence of at least...
Obstructive sleep apnea is an increasingly well recognized disease
characterized by periodic collapse of the upper airway during sleep.
Obstructive sleep apnea (OSA) is characterized by periodic complete or
partial upper airway obstruction during sleep, causing intermittent
cessations of breathing or reductions in airflow despite ongoing
respiratory effort. It’s defined by the presence of at least 5 obstructive
apneas, hypopneas, or both per hour while the patient is sleeping.[1]
The goals of the treatment of OSA should be aimed at alleviating
symptoms while decreasing morbidity and mortality in a manner that
minimizes side effects, For example approximately 70% of patients with OSA
are obese. It has been shown that weight loss improves and in some cases
cures sleep-related breathing disorders and is dearly a low morbidity
treatment modality.[2,3] it also has been shown, however. That the
improvement in apnea-hypopnea index (AHI) with weight loss. Particularly
in moderate to severe sleep apnea. is only partial.[4]
Many surgical procedures have been described during the last 20
years. but of these procedures. Uvulopalatopharyngoplasty (UPPP) first
described in 1981 by Fujita et al.[5]
Determining the site of obstruction is problem for choice the
surgical procedure. accurate identification of the exact sites of
collapse should aid the surgeon in procedure selection, thereby improving
success rates. The difficulty in precisely determining the anatomic site
of obstruction in patients with OSA leads to challenges in predicting
which patients will benefit from palatal surgery in isolation.
Owing to the difficulty in predicting a single site of obstruction
with relative accuracy most surgeons currently advocate a multiphase
approach in the surgical treatment of OSA, with UPPP playing an integral
role. Increased success rates are seen when multiple procedures are med
that address various sites of obstruction.[6,7]
UPPP in the surgical management of OSA would be incomplete without
mentioning the complications of the procedure and its associated
morbidity.
Vestbo et al. did an interesting secondary analysis of the results of
the Tristan study in outpatients aged 40-70 years, with COPD (FEV1= 25-70%
predicted, and reversibity...
Vestbo et al. did an interesting secondary analysis of the results of
the Tristan study in outpatients aged 40-70 years, with COPD (FEV1= 25-70%
predicted, and reversibity <_10 predicted="predicted" fev1.="fev1." treatment="treatment" with="with" salmeterol="salmeterol" fluticasone="fluticasone" _50="_50" _500mcg="_500mcg" bd="bd" was="was" within="within" two="two" weeks="weeks" superior="superior" and="and" alone="alone" to="to" placebo.1="placebo.1" furthermore="furthermore" a="a" beneficial="beneficial" effect="effect" breathlessness="breathlessness" scores="scores" pefr="pefr" fev1="fev1" of="of" did="did" predict="predict" the="the" outcome="outcome" continuous="continuous" for="for" _1="_1" year="year" in="in" most="most" patients.="patients." p="p"/>These findings have implications for primary care. We have the following
questions that all regard the selection of patients in primary care that
may benefit inhaler therapy for COPD.
First, the lung function was measured as ‘clinic FEV1’. Was the flow-
volume loop used? And furthermore was the ‘clinic’ measurement of FEV1
done with an instrument equipped with a turbine system with rotating vane,
that is commonly used in primary care settings? Or, was a pneumotachometer used, which seems to be the gold standard in
the lung function laboratory? Could a difference between ‘clinic FEV1’ and
FEV1 measured in a lung function laboratory have biased the results of the
study?
Second, 746 out of the 1465 participants were current smokers. The
efficacy of inhaled corticosteroids (ICS) is diminished in smokers with
asthma.[2] An effect on symptoms of the lower airways of ICS for two weeks
was missing in smoking non-asthmatic adults who presented persistent
cough to the general practitioner.[3] This is in line with the finding of
Cox et al. that for four weeks treatment with ICS did not affect cigarette
smoke-induced inflammation in current smokers without airflow
obstruction.[4] Therefore, reanalysis of the current data while comparing
the short-term outcomes (within two weeks) in smokers vs. non-smokers
could be of interest.
Third, a further analysis by severity of COPD is needed. For it was
suggested that treatment of patients with chronic bronchitis and almost
normal lung function (mean FEV1 95% of the predicted value (SD18%)) with
fluticasone 250 mcg b.i.d does have a short term but no long term
effect.[5] Do patients with more severe COPD show a better short as well
as a better long term response to treatment with inhalers , compared with
patients with les severe COPD?
Further controlled trials of treatment in less severe COPD-patients in
primary care with ICS, long acting beta2 agonists, anticholinergic drugs,
and their combinations, could be needed. Then, symptom scores should
include not only the breathlessness scores that were used in the current
analysis, but also cough scores. Cough is a prominent symptom in the early
stages of COPD.
Fourth, patients with early stages of COPD in primary care show
intermittent or episodic symptoms: ‘exacerbations’. It is thought that
salmeterol/fluticasone combination treatment in particular induces rapid
improvement in lung function, enhances exercise tolerance and reduces the
perceived severity of exacerbations.[6] However, combination therapy did
not significantly improve exacerbation rate compared with salmeterol or
fluticasone alone. Therefore, the therapeutic regimens to be studied
should concentrate upon short term effects of treatments. Further, the
predictive value of the short term treatment effects for long term
outcomes has to be studied. The current analysis made a first move for
that.
Lastly, intermittent, symptomatic or ‘as needed’ inhaler treatments
for COPD must to be compared with continuous long term treatments as
studied by Vestbo et al. This approach is supported by the recent findings
that the outcomes of as-needed treatment with ICS in adults with mild
persistent asthma, in terms of morning PEFR or number of exacerbations,
was not different from sustained treatment for one year.[7]
Finally, we hypothesize that the potential of salmeterol/fluticasone in
COPD is in the exacerbation of non-smokers. If so, the ‘as-needed’ use of
combination inhaler therapy for COPD it may optimise the benefit/side
effects and benefit/cost ratio’s.
References
1. Vestbo J, Pauwels R, Anderson JA, Jones P, Calverley P. Early onset of
effect of salmeterol and fluticasone propionate in chronic obstructive
pulmonary disease.
Thorax. 2005;60:301-4.
2. Piipari R, Jaakkola JJ, Jaakkola N, Jaakkola MS. Smoking and asthma in
adults. Eur Respir J. 2004;24:734-9.
3. Ponsioen BP, Hop WC, Vermue NA, Dekhuijzen PN, Bohnen AM. Efficacy of
fluticasone on cough: a randomised controlled trial. Eur Respir J. 2005
;25:147-52.
4. Cox G, Whitehead L, Dolovich M, Jordana M, Gauldie J, Newhouse MT. A
randomized controlled trial on the effect of inhaled corticosteroids on
airways inflammation in adult cigarette smokers. Chest. 1999;115:1271-7.
5. van Grunsven P, Schermer T, Akkermans R, Albers M, van den Boom G, van
Schayck O, van Herwaarden C, van Weel C. Short- and long-term efficacy of
fluticasone propionate in subjects with early signs and symptoms of
chronic obstructive pulmonary disease. Results of the DIMCA study. Respir
Med. 2003;97:1303-12.
6. Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A, Anderson
J, Maden C; TRial of Inhaled Steroids and long-acting beta2 agonists study
group. Combined salmeterol and fluticasone in the treatment of chronic
obstructive pulmonary disease: a randomised controlled trial. Lancet.
2003;361:449-56.
7. Boushey HA, Sorkness CA, King TS, Sullivan SD et al. Daily versus as-
needed corticosteroids for mild persistent asthma. N Engl J Med.
2005;352:1519-28.
Vestibo et al. report their surprise at the rapid effect of inhaled
fluticasone propionate (FP) on symptoms of dyspnoea and PEFR improvements
in COPD subjects.[1] A feasible explanation for their observation is
suggested by considering the effects of FP on airway vascular biology in
asthmatic and healthy individuals. The impressive work by Wanner et al.
demonstrated that FP causes acute vasoconstrict...
Vestibo et al. report their surprise at the rapid effect of inhaled
fluticasone propionate (FP) on symptoms of dyspnoea and PEFR improvements
in COPD subjects.[1] A feasible explanation for their observation is
suggested by considering the effects of FP on airway vascular biology in
asthmatic and healthy individuals. The impressive work by Wanner et al.
demonstrated that FP causes acute vasoconstriction (maximal at 30 minutes)
in the bronchial mucosa, as measured by the validated dimethyl ether
uptake technique.[2] The mechanism is believed to be glucocorticoid-
mediated enhancement of airway adrenergic and noradrenergic
neurotransmission.[3] This acute vasoconstrictor response results in
mucosal decongestion and reduced clearance of beta agonist from the
airway. Both of these effects serve to reduce airflow obstruction as
measured by patient symptoms and PEFR. The findings of Vestibo and
colleagues suggest inhaled corticosteroid produce a similar effect in the
COPD airway that may be of immediate benefit to the patient.
References
1. Vestibo J, Pauwels R, Anderson JA, et al. Early onset of effect of
salmeterol and fluticasone propionate in chronic obstructive pulmonary
disease.Thorax 2005;60:301-304.
2. Kumar SD, Brieva JL, Danta I, et al. Transient effect of inhaled
fluticasone on airway mucosal blood flow in subjects with and without
asthma. Am. J. Respir. Crit. Care Med. 2000;161:918-921.
3. Chang PC, van der Krogt JA, and van Brummelen P. Demonstration of
neuronal and extraneuronal uptake of circulating norepinephrine in the
forearm. Hypertension 1987;9:647-653.
The paper by Hessel and colleagues is a valuable summary of the
somewhat conflicting literature concerning asbestos exposure and lung
cancer risk in the absence of a clinical diagnosis of asbestosis. The
authors rightly point out that the risk of lung cancer may be very
different in patients exposed to different fibre types and with different
degrees of fibrosis ranging from severe fibrosis on plain...
The paper by Hessel and colleagues is a valuable summary of the
somewhat conflicting literature concerning asbestos exposure and lung
cancer risk in the absence of a clinical diagnosis of asbestosis. The
authors rightly point out that the risk of lung cancer may be very
different in patients exposed to different fibre types and with different
degrees of fibrosis ranging from severe fibrosis on plain chest
radiographs to subtle localized fibrosis on a high resolution CT scan or
at autopsy.
However, one feature of the civil medicolegal system was not
mentioned. Civil courts make awards on the "balance of probability", not
on the basis of relative risk. For example, the study of Hillerdal
(reference 8) showed that the relative risk of lung cancer in patients
with pleural plaques was 2.3 if the patient had radiographic evidence of
asbestosis and 1.4 in the absence of asbestosis. This study involved 1596
men and provided strong evidence of an association between pleural plaques
and increased risk of lung cancer. However, on a "balance of probability
test", only those with asbestosis (relative risk above 2.0 ) would be
judged to have lung cancer that was the direct result of previous asbestos
exposure. Patients with plaques but no evidence of asbestosis may have a
40% increased risk of lung cancer compared with somebody not exposed to
asbestos but they would not be compensated because the balance of
probability in individual cases would not favour an asbestos attributable
cancer.
Dear Editor,
I have been working on the twitch pressure of mouth, diaphragmatic and tracheal (airway) for several years and had done the work about the relationship between the twitch pressure of mouth or the twitch pressure of tracheal and twitch pressure of diaphragmatic in ventilated patients because of respiratory failure or during general anaesthesia because of abdomen operation. Recently, when I read of t...
Dear Editor,
I would like to share my views again after hearing from you that what clinical criteria and biochemical parameters for the remission in asthma have been used in your study. What partameters were compared for the asthma remission in spirometery values pre and post remission phases.
In the complete clinical remission what predictors have been taken into consideration for the remission. No doubt remi...
Dear Editor,
It is generally appreciated that the practice of stepping-down inhaled corticosteroid (ICS) therapy in patients with stable asthma is poorly implemented, albeit in the background of limited evidence.1 Indeed, the appreciation for stepping-down ICS therapy once asthma control is attained is well established within the Global Initiative for Asthma (GINA) guidelines2 and has recently been...
Dear Editor,
The authors of the UK guidelines on asthma have asked for feedback based on audit.[1] The latest British guidelines for asthma management suggest that children with moderate exacerbation of asthma presenting to the accident and emergency unit (annexure 5) must be treated with beta agonists: 2 to 10 puffs via a spacer and re-assed after 15 minutes. This recommendation seems to be observed often in the...
Dear Editor,
We read with interest your approved guidance on the key issues which should be considered in preparing a genetic association studies to become acceptable for publication in Thorax [1-2]. While we agree with several points in this guidance, there are still several other points that we see as exaggerated or at best controversial.
We even can see that in the eight genetic association studies p...
Dear Editor,
The combination of acute and chronic haemondynamic effects in obstructive sleep apnea have been associated with increased risk of myocardial infarction, cerebrovascular accidents, hypertension, and congestive heart failure. It is necessary to provide appropriate treatment for Obstructive sleep apnea syndrome (OSAS).
Most health care providers offer nasal continuous positive airway pressure...
Dear Editor,
Obstructive sleep apnea is an increasingly well recognized disease characterized by periodic collapse of the upper airway during sleep. Obstructive sleep apnea (OSA) is characterized by periodic complete or partial upper airway obstruction during sleep, causing intermittent cessations of breathing or reductions in airflow despite ongoing respiratory effort. It’s defined by the presence of at least...
Dear Editor,
Vestbo et al. did an interesting secondary analysis of the results of the Tristan study in outpatients aged 40-70 years, with COPD (FEV1= 25-70% predicted, and reversibity...
Dear Editor,
Vestibo et al. report their surprise at the rapid effect of inhaled fluticasone propionate (FP) on symptoms of dyspnoea and PEFR improvements in COPD subjects.[1] A feasible explanation for their observation is suggested by considering the effects of FP on airway vascular biology in asthmatic and healthy individuals. The impressive work by Wanner et al. demonstrated that FP causes acute vasoconstrict...
Dear Editor,
The paper by Hessel and colleagues is a valuable summary of the somewhat conflicting literature concerning asbestos exposure and lung cancer risk in the absence of a clinical diagnosis of asbestosis. The authors rightly point out that the risk of lung cancer may be very different in patients exposed to different fibre types and with different degrees of fibrosis ranging from severe fibrosis on plain...
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