As Professor Treasure observed in his editorial written in the BMJ
this week pneumonectomy for cancer still has a postoperative mortality of
10% to 15% despite patients being rejected if their respiratory function
is limited.
Patients who cannot climb stairs before a pneumonectomy had
"similar morbidity rates (31.1 vs. 35.6%, respectively, P=0.7), but higher
mortality rates (15.6 vs. 4....
As Professor Treasure observed in his editorial written in the BMJ
this week pneumonectomy for cancer still has a postoperative mortality of
10% to 15% despite patients being rejected if their respiratory function
is limited.
Patients who cannot climb stairs before a pneumonectomy had
"similar morbidity rates (31.1 vs. 35.6%, respectively, P=0.7), but higher
mortality rates (15.6 vs. 4.4%, respectively, P=0.08) and deaths among
complicated patients (50 vs. 12.5%, respectively, P=0.025)", [occur]
compared to matched controls who could perform a stair climbing test
bfore pneumonectomy [1]. These data might be interpreted as support for
even more stringent selection criteria. That would be a pity for
radiotherapy is not as effective as definitive surgery.
Half the postoperative deaths after a pneumonectomy are attributable
to bronchopleural fistulae and its subsequent complications. This
complication is more likely to occur on the right than the left. There
are technical reasons for this notably the increased need for a hand-sewn
anastomosis. Smoking remains an important risk factor [2].
It is a long time since I spent 6 months as Mr Bromley's houseman at
St Mary's but recall well the technical challenges, postoperative fears
and the hazards of postoperative care. May I offer some observations and
suggestions. My thoracic credentias are that I do not recall ever having
had a death within 30 days of an oesophagectomy regardless of the
approach, mostly transhiatal for lower third lesions, or manner of
construction.
The break down of a broncheal stump closure may have technical
origins but almost certainly also have a metabolic origin, namely an
energy supply/demand imbalance imposed by local, regional, and/or
systemeic causes. Regional causes might include cytokine release which can
iinhibt oxygen consumption, convert xanthine dehydrogenase into xanthine
oxidase, deplete adenine nucleotide pools, and promote free radical
release. Blood products administered intravenously and especially those
from incomplete haemostasis in the viscinity of the bronchial stump might
be the most important early causes of cytokine release and sepsis a later
cause.
Whilst cytokines may increase net ATP yield by uncoupling and
increasing metabolic rate they might only be able to do so if blood flow
can be greatly increased to acccommodate the increased demand for nutrient
delivery and uptake to compensate for the accmpanying decline in
efficiency of ATP resynthesis. The adequucy of hepatic oxygenation appears
to be critical for this to be sustained in hyperperfused healing wounds.
ATP resynthesis in a healing wound appears to be almost solely dependent
upon anaerobic glycolysis, rather than oxidative phosphorylation, and the
ability to wash tissue metabolites out of the wound and recycle them in
the liver. The perceived need for positive pressure ventilation and
especially PEEP might aid in the generation of the pressure ultimately
responsible for blowing a stump whose tissue energeticss have been
compromsied.
Several stragegies might be conveniently adopted. Meticulous
attention to haemostasis. The avoidance of transfusion with blood products
at any stage even if the haemoglobin falls. The avoidance of increasing
the FiO2 for this might increase the risk of pulmonary damage by
increasing free radical release. Supplementary oxygenation delivered
transenteraly and/or transperitoneally to achieve adequate hepatic
oxygenation, increase arterial oxygen daturation, decrease myocardial
workload, and avoid the ned for positive pressure ventilation and
especially PEEP [3]. ECMO might even be of supplementary benefit in this
regard.
Dead spaces are notorious for their propensity to become secondarily
infected especially if needles are inserted into them as was done
routinely and repetitively to prevent mediastinal drift after pneumonetomy
when I was a houseman. Might the dead space be effectively closed by
incising or even excising the diaphragm, rotatng the liver and allowing
the abdominal contents to enter the thorax? The diaphragm is no longer
needed and any continued contractions permitted might even increase the
risk of cytokine release. Mediastnal drift could not occur if the right
lobe of the liver was ocupying the space. If in addition the omentum were
mobilized, making sure not to devasculrize a part of it [easy to do and
difficult to recognize because it may not turn blue], it might even be
used to buttress the stump and alllow it to benefit from its unique
properties. Havimg said that I never did that for my intestinal
anastomoses and never had a fatal leak even one I had in the chest.
Drains, other than closed suction drains, appar to have an adverse
effect inthe abdomen by increasing the risks of infection. I adandoned the
practice of placng a drain next to a colonic or rectal anastmosis and
closing the floor of the pelvis very early in my career and never had a
reason to regreet the practice. I even dispensed with the prctive of
placng a chest drain after a Sigura I did through the left chst. I would
give serious consideration, therefore, to avoiding the use of any forms of
drains after a pneumonectomy.
The major added risks might be kinking the cava and intestinal
obstruction but with full mobilization of the liver these should be easy
to avoid. The liver and heart transplant surgeons might have the best
technical advice to offer in this regard. My two cents would be to cleanse
the gut before surgery with a lavage, and make sure that al intraabdominal
adhesions are feed from DJ flexure to ileocaeca valve and that the small
bowel is placed in its proper anatomic position prefrable with an intact
omentum placed over it under the wound.
The potential for increasing the number of patients who might
withstand a pneumonectomy in additon to reducing the risks of surgery by
supplementary oxygenation via transenteral and/or peritoneal routes would
seem huge. In our animal study we were able to able to completely abolish
the compensatory increase in cardiac output induced by very severe
hypoxaema. We did this by tranenteral oxygenation of juat some 60% of the
small bowel. The obvious concern would be perforation but that risk would
be small if a transperitoneal route were employed as exprience with
peritoneal dilaysis has shown.
There is one other intervention that might increase the efficiency of
ATP resynthesis by oxidarive phosporylation and limit myocardial workload
and hence risk of MI during and afrer surgery. Clamping actual gastic
intramucosal pH at abnormaly low levels wiht a Radiometer pH-stat system
whilst keeping the standard intramucosal pH at 7.40 [4].
I see no reason why resection rates might not be increased and 30-day
mortality from pneumonectomy reduced to less than 1% by experimenting
with these strategies.
The possibility that transenteral oxygenation might also be safely
achieved on a chronic basis and increase the quality of life after
pkeumonectomy, or indeed in anyone with limited pulmonar function, would
seem very real [5].
References:
1. Brunelli A, Sabbatini A, Xiume' F, Borri A, Salati M, Marasco RD,
Fianchini A. Inability to perform maximal stair climbing test before lung
resection: a propensity score analysis on early outcome.
Eur J Cardiothorac Surg. 2005 Mar;27(3):367-372.
2. Darling GE, Abdurahman A, Yi QL, Johnston M, Waddell TK, Pierre A,
Keshavjee S, Ginsberg R. Risk of a right pneumonectomy: role of
bronchopleural fistula.
Ann Thorac Surg. 2005 Feb;79(2):433-7.
3. Gross BD, Sacristan E, Peura RA, Shahnarian A, Devereaux D, Wang
HL, Fiddian-Green R Supplemental systemic oxygen support using an
intestinal intraluminal membrane oxygenator.
Artif Organs. 2000 Nov;24(11):864-9.
Dr Leckridge[1] is correct to state that the children in the study had
mild to moderate symptoms of asthma at the time of recruitment. Children
with more severe symptoms were excluded at the request of the Ethics
Committee, because of the risks that could arise if they stopped their
conventional medication. Our study tested homeopathy as an adjunct to
standard medical management, not an alternative.
Dr Leckridge[1] is correct to state that the children in the study had
mild to moderate symptoms of asthma at the time of recruitment. Children
with more severe symptoms were excluded at the request of the Ethics
Committee, because of the risks that could arise if they stopped their
conventional medication. Our study tested homeopathy as an adjunct to
standard medical management, not an alternative.
We expected that children
given homeopathy might be able to reduce their conventional medication by
standard guidelines, but could not find any evidence that this occurred.
We acknowledged that there were trends in favour of the homeopathy group
in some measures, but not in the primary measure, which was recommended by
the questionnaire’s author as the most sensitive to change. We were
careful not to over-generalise from our study, and certainly did not claim
that homeopathy is ineffective in different samples of patients with
asthma, for example those with more severe symptoms.
Reference
(1) Leckridge R. Homeopathy and childhood asthma [electronic response to White et al. Individualised homeopathy as an adjunct in the treatment of childhood asthma: a randomised placebo controlled trial] thoraxjnl.com 2003 http://thorax.bmjjournals.com/cgi/eletters/58/4/317#59
Lung cancer accounts for 1 in 3 cancer deaths and 25% of cancer registrations. Recognition that accurate and prompt diagnosis can help save lives has led to the formation of the multidisciplinary team (MDT), which consists primarily of chest physicians, thoracic surgeons, radiologists, pathologists, and oncologists, in the management of patients with lung cancer.
Lung cancer accounts for 1 in 3 cancer deaths and 25% of cancer registrations. Recognition that accurate and prompt diagnosis can help save lives has led to the formation of the multidisciplinary team (MDT), which consists primarily of chest physicians, thoracic surgeons, radiologists, pathologists, and oncologists, in the management of patients with lung cancer.
A study was conducted to assess the effectiveness of the lung cancer MDT. Data were compared between the year 1997 and 2003 representing the pre- and post-MDT era respectively.
Data are shown in Table 1.
Establishment of the MDT has lead to significant improvements in lung cancer outcomes and is effective in managing patients with lung cancer.
Table 1. Data for the year 1997 (pre-MDT) and 2003 (post-MDT).
One of the paradoxes of modern medicine is the rapid growing
incidence of immune-based diseases over the last half of the century.
Despite enormous advances in our understanding of the immune system, and
our ability to manipulate immunity in experienced animals and man, we have
not been able to curtail these diseases. In fact, it is becoming
increasing evident that immune hypersensitivity response...
One of the paradoxes of modern medicine is the rapid growing
incidence of immune-based diseases over the last half of the century.
Despite enormous advances in our understanding of the immune system, and
our ability to manipulate immunity in experienced animals and man, we have
not been able to curtail these diseases. In fact, it is becoming
increasing evident that immune hypersensitivity responses are central to
the pathogenesis of many of the most common diseases of the 21st century
including atherosclerosis, diabetes, obesity, and arthritis . Included in
this epidemic are atopy-associated disorders (such as asthma, eczema,
allergic rhinoconjunctivitis, and food allergies), which have skyrocketed
in prevalence. While genetic factors certainly contribute to the
pathogenesis of these diseases, there is emerging evidence that their
rising incidence is related to changes in western lifestyle. ADAM 33, a
new asthma gene is a major breakthrough and would definitely help in the
management of asthma.
Dr Toma and colleagues [1] describe interesting directions along which
fibreoptic bronchoscopy may develop. The authors quite rightly state that
rigid bronchoscopy has largely fallen within the domain of thoracic
surgeons. Furthermore the techniques available until relatively recently
were limited. I think it appropriate to ask the question “will this
situation change”? In my opinion it already has...
Dr Toma and colleagues [1] describe interesting directions along which
fibreoptic bronchoscopy may develop. The authors quite rightly state that
rigid bronchoscopy has largely fallen within the domain of thoracic
surgeons. Furthermore the techniques available until relatively recently
were limited. I think it appropriate to ask the question “will this
situation change”? In my opinion it already has. At St George’s Hospital
we have a multidisciplinary team approach to investigate and treat
patients with diverse large airway pathologies. There is input from
specialists in cardiothoracic surgery, anaesthesia, medicine and intensive
care and respiratory medicine. Our procedures are performed in a
cardiothoracic theatre on a designated morning list. Theatre personnel
involved include a consultant in cardiothoracic anaesthesia with SpRs in
anaesthesia, a consultant in cardiothoracic medicine, SpRs in respiratory
medicine and a research fellow. In addition there is full nursing and
operating department assistant support.
We regularly receive referrals of
patients with severe large airway compromise who present a challenging
anaesthetic risk. We perform approximately 20 endobronchial intervention
procedures (Nd Yag laser therapy, endobronchial stent deployment for
benign and malignant diseases, dilatation techniques, foreign body
retrieval, biopsies of proximal friable tumours and paediatric
interventions e.g. localisation of tracheo oesophageal fistula in
neonates) per month. Our trainees in respiratory medicine spend an
initial period of three months in our unit. They gain excellent exposure
to large airway intervention, receive training in rigid bronchoscopic
deployment in a controlled environment and have exposure to the large
number of interventions currently available.
We consistently receive positive feedback from our SpRs in
respiratory medicine and indeed regularly welcome visitors from overseas.
The use of an intra-operative video is a useful teaching tool and the work
also provides an important forum for research. Our SpRs advise us that
skills learnt in deployment of the rigid bronchoscope gives them extra
confidence for their fibreoptic bronchoscopy work. Additionally the fact
that there are cardiothoracic surgeons available in theatre provides an
important opportunity to discuss patients with colleagues in thelight of
the bronchoscopic appearances and in conjunction with radiology (available
on PACS in theatre).
Over the past five years we have had no operative mortality. Two
patients developed a pneumothorax which required intercostal chest drain
deployment. Although bleeding was encountered occasionally it was always
possible to secure haemostasis by endobronchial means including direct
application of adrenalin on gauze using rigid forceps. We never cease to
be amazed by the spectrum of referrals which we are privileged to receive.
Indeed on last weeks list alone there was one patient with tracheal
amyloid causing 90% obstruction who was treated using Nd Yag laser
therapy, a patient with adenoid cystic carcinoma referred by our oncology
colleagues also for tumour debulking using Nd Yag laser, dilatation of an
airway stricture in a patient with Wegener’s granulomatosis, deployment of
a right main bronchial stent in a patient with extrinsic airway
compression as a consequence of achalasia of the oesophagus and removal of
a right main bronchial lipoma which was obstructing the right main
bronchus completely.
With increasing demand from trainees in respiratory medicine,
thoracic surgery and anaesthesia to learn these techniques we arrange
national study days for endobronchial intervention on a biannual basis.
I believe that there is a brave new world for interventional
bronchoscopy but given our experience together with the very positive
feedback from our trainees I believe that rigid bronchoscopy and large
airway intervention should have an important and more prominent role among
respiratory physicians in this new world.
Yours sincerely.
Dr Brendan Madden, MD, MSc, FRCP, FRCPI
Consultant Cardiothoracic and ITU Physician
Reader in Cardiothoracic Medicine
Reference
1. Toma TP, Geddes DM, Shah PL. Thorax 2005; 60:180–181
With great interest, we read the guidelines for the management of
suspected acute pulmonary embolism (PE) by the British Thoracic Society
(June issue 2003).[1] In the discussion of treatment options, the
guidelines state that surgical embolectomy should only be considered in
cases with absolute contraindications to thrombolysis, which is rarely an
important consideration in a life-threatening situat...
With great interest, we read the guidelines for the management of
suspected acute pulmonary embolism (PE) by the British Thoracic Society
(June issue 2003).[1] In the discussion of treatment options, the
guidelines state that surgical embolectomy should only be considered in
cases with absolute contraindications to thrombolysis, which is rarely an
important consideration in a life-threatening situation.
In contrast to the guidelines, a recent study of surgical pulmonary
embolectomy with the use of normothermic cardiopulmonary bypass
liberalized these criteria. Patients with anatomically extensive pulmonary
embolism and concomitant right heart failure were included and
demonstrated a 1-month mortality rate of only 11% following surgical
intervention.[2] The improved survival rates in this case series as
compared to previous reports [3,4] may be related to advances in surgical
technique, patient selection and the experience of cardiac surgeons and
cardiac anesthesiologists with this operation. However, this report no
longer confines surgical pulmonary embolectomy to a treatment of last
resort reserved for clinically desperate circumstances. In contrast,
centers that are experienced in performing pulmonary embolectomy may
consider utilizing this therapeutic intervention more liberal in order to
improve morbidity and mortality of patients suffering from severe PE.
References
(1) British Thoracic Society guidelines for the management of
suspected acute pulmonary embolism. Thorax 2003;58(6):470-483.
(2) Aklog L, Williams CS, Byrne JG, Goldhaber SZ. Acute Pulmonary
Embolectomy: A Contemporary Approach. Circulation 2002;105(12):1416-1419.
(3) Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ,
3rd. Predictors of survival after deep vein thrombosis and pulmonary
embolism: a population-based, cohort study. Arch Intern Med 1999;159(5):445-53.
(4) Doerge H, Schoendube FA, Voss M, Seipelt R, Messmer BJ. Surgical
therapy of fulminant pulmonary embolism: early and late results. Thorac
Cardiovasc Surg 1999;47(1):9-13.
Re: Symptoms and the early diagnosis of lung cancer
Five year survival of patients with Lung Cancer in the United Kingdom is disappointing and the comparisons made by Birring et al. [1] and others with
some internationally published data have been consistently unfavourable [2].
Doctors and government bodies in the United Kingdom have searched for
differences in patients, disease or treatmen...
Re: Symptoms and the early diagnosis of lung cancer
Five year survival of patients with Lung Cancer in the United Kingdom is disappointing and the comparisons made by Birring et al. [1] and others with
some internationally published data have been consistently unfavourable [2].
Doctors and government bodies in the United Kingdom have searched for
differences in patients, disease or treatment which might explain the
shortfalls in survival and improve the care of our patients [2,3]. There has
been little focus in the literature on the data. Review of the SEER
website 5 year survival figure referenced by Birring et al. and others
throws some light on the survival differences. In their latest survival data SEER report 64,035 cases of non small cell lung cancer, 11,306 cases
of small cell lung cancer and 75,341 of lung and bronchus cancer [4]. It can
only be assumed that cases without proven histology are not included in
the much quoted SEER lung and bronchus cancer survival figures. Survival
figures for lung cancer in the United Kingdom do include around 25% of
cases without histology [5]. Survival of patients diagnosed as having lung
cancer without proven histology is around a quarter of those with proven
histology. Cancer registry data suggest leaving these patients out of the
survival calculation will add around 4% to survival at 5 years [5]. SEER data
cannot therefore be used to compare overall survival in the United Kingdom
with that of the United States.
Wendy JA Anderson
Claire Butler
Karen Darragh
Graeme P Currie
References
1. Birring S S, Peake M D. Five year survival of patients with Lung Cancer in the United Kingdom. Thorax 2005;60 268-269.
2. Sikora K. Cancer survival in Britain. Bmj 1999;319:461-2.
3. Improving Outcomes in Lung Cancer: The Manual. Department of Health,
1998.
5. Fitzpatrick D, Gavin A, Middleton R, Catney D. Cancer in Northern
Ireland 1993-2001. A Comprehensive report. Northern Ireland Cancer
Registry. Queens University Belfast, 2004.
We would like to comment on strength of conclusions of the recent
publication by Dr Brusasco et al,[1] particularly that no consideration
is given to how the results compare to the balance of evidence that
exists.
The paper’s conclusions imply superior efficacy of tiotropium over
salmeterol in patients with COPD by emphasising endpoints in which
tiotropium shows a difference compar...
We would like to comment on strength of conclusions of the recent
publication by Dr Brusasco et al,[1] particularly that no consideration
is given to how the results compare to the balance of evidence that
exists.
The paper’s conclusions imply superior efficacy of tiotropium over
salmeterol in patients with COPD by emphasising endpoints in which
tiotropium shows a difference compared with placebo, but salmeterol does
not. However, as this combined analysis fails to show clinically relevant
differences between salmeterol and tiotropium we believe such conclusions
to be somewhat exaggerated.
We note that for certain endpoints, salmeterol in this analysis
failed to show a difference compared with placebo. While these results
were disappointing, they are not reflective of the wealth of evidence that
exists from previous placebo-controlled studies of up to 12 months
duration with salmeterol. These studies show significant improvements in
lung function, quality of life, breathlessness and reliever use, and
exacerbations compared with placebo/usual therapy.[2-9]
A recent meta-analysis of nine double-blind studies including over
3500 patients with COPD confirms that salmeterol has a significant and
sustained bronchodilator effect with no evidence of tolerance compared
with placebo, and significantly reduces the risk of exacerbations (22%
reduction compared with placebo/usual therapy).[9,10]
Lastly, and we feel importantly, this study and analysis introduces a
new definition of COPD exacerbations with no explanation for the
rationale, nor a justification for the validity of this. Previous studies
have either used health utilisation [2,11] (event measured is sufficiently
important for the patient to seek medical help and the physician to feel
the patient needs treatment), or exacerbations are defined by a
combination of major and minor symptoms.[12,13] By not using any of these
definitions, it is difficult for the clinician to evaluate any relative
efficacy of tiotropium in reducing exacerbations, compared to other
therapeutic agents currently available.
In conclusion, it is important to reflect on whether the findings of
this study are supported by what we already know. We feel it is important
to state that for this publication and for the results seen for
salmeterol, this is clearly not the case.
References
(1) Brusasco V, Hodder R, Miravitlles M, Korducki L, Towse L, Kesten S.
Health outcomes following treatment for six months with once daily
tiotropium compared with twice daily salmeterol in patients with COPD.
Thorax 2003;58:399-404.
(2) Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and
fluticasone in the treatment of chronic obstructive pulmonary disease: a
randomised controlled trial. Lancet 2003;361:449–456.
(3) Mahler DA, Wire P, Horstman et al. Effectiveness of fluticasone
propionate and salmeterol combination delivered via the Diskus device in
the treatment of chronic obstructive pulmonary disease. Am J Respir Crit
Care Med 2002;166:1084-1091.
(4) Hanania NA, Knobil K, Watkins M, Wire P, Yates J, Darken P. The efficacy
and safety of fluticasone propionate 250mcg/salmeterol 50mcg combined in
the Diskus inhaler for the treatment of chronic obstructive pulmonary
disease. Chest 2003;in press.
(5) Stockley RA, Chopra N. Salmeterol, added to usual therapy is an
effective bronchodilator over 12 months of treatment in chronic
obstructive pulmonary disease (COPD). Eur Respir J 2002;20 (suppl
38):241s.
(6) Stockley RA, Davies EA, Sondhi S, Rice L. Salmeterol provides sustained
health status improvement over 12 months in patients with COPD. Eur Respir
J 2002;20(suppl 38):241s.
(7) Jones PW, Bosh TK. Quality of life changes in COPD patients treated with
salmeterol. Am J Respir Crit Care Med 1997;155:1283–1289.
(8) Boyd G, Morice AH, Pounsford JC, Siebert M, Peslis N, Crawford C. An
evaluation of salmeterol in the treatment of chronic obstructive disease.
Eur Respir J 1997;10(4):815–821.
(9) Stockley RA, Whitehead PJ, Williams MK, Hagan G. Serevent 50mcg bid
significantly reduces moderate-severe exacerbations in patients with all
severities of COPD. Am J Respir Crit Care Med 2003;167(7):A949.
(10) Stockley RA, Whitehead PJ, Williams MK, Hagan G. Serevent 50mcg bid
significantly increases trough FEV1 in COPD up to 12 months without loss
of effect. Am J Respir Crit Care Med 2003;167(7):A95.
(11) Szafranski W, Cukier A, Ramirez A et al. Efficacy and safety of
budesonide/formoterol in the management of chronic obstructive pulmonary
disease. Eur Respir J 2003;21:74-81.
(12) Anthonisen RN, Manfreda J, Warren CPW, Hershfield ES, Harding GKM,
Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive
pulmonary disease. Ann Intern Med 1987;106:196-204.
(13) Seemungal TAR, Donaldson GC, Bhowmik A et al. Time course and recovery
of exacerbations in patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med 2000;161:1608-1613.
In his letter, Dr Devoy is questioning the strength of the conclusion in our publication regarding the clinical efficacy of salmeterol on dyspnea, quality of life and reductions of exacerbations.
We had stated that the effects with long-acting ß2-adrenergic
bronchodilators on COPD exacerbations and on other health outcomes has
provided inconsistent results [1] We note that Dr Devoy’s argument is
mo...
In his letter, Dr Devoy is questioning the strength of the conclusion in our publication regarding the clinical efficacy of salmeterol on dyspnea, quality of life and reductions of exacerbations.
We had stated that the effects with long-acting ß2-adrenergic
bronchodilators on COPD exacerbations and on other health outcomes has
provided inconsistent results [1] We note that Dr Devoy’s argument is
mostly based on two studies published very recently, one shortly before [2] and one at the same time [3] of our study, on one paper in press and
four abstracts. We believe it is optimal to restrict comments only to the
evidence arising from published full peer-reviewed papers. The recent
study by Mahler et al.[2] referenced by Dr Devoy showed no difference
between salmeterol and placebo regarding dyspnea, exacerbations, or health
status. A similar lack of efficacy on these health outcomes was observed
by Rennard et al.[4] Calverley et al.[3] showed slightly less
exacerbations, but no effects with regard to quality of life and dyspnea.
These findings do not change, but rather reinforce, our opinion that
salmeterol treatment in COPD gave inconsistent results.
Dr Devoy further questions the definition of exacerbations of COPD
used in our analysis, suggesting the use of health utilization or a
combination of major and minor symptoms. There is no general consensus
and a range of definitions have been used in the literature. Indeed, in at
least three studies describing the effect of salmeterol on exacerbations,
no definition at all is provided.[2,4,5] In our study, the definition of
exacerbation has been pre-specified, includes a minimal time frame (3
days) to eliminate the misinterpretation of day to day variability and
requires a minimum of two symptoms (new onset or increase in symptoms).
Using this exacerbation definition, 88-91% of COPD exacerbations in this
trial required the use of either antibiotics or oral corticosteroids or
both, indicating that the clinicians involved considered the vast majority
of these flare-ups to be clinically significant. The reduction seen with
tiotropium in our study is also supported by the reductions in COPD
exacerbations and associated hospitalizations observed in one-year trials,
the later outcome (hospitalizations) being an important outcome with
little debate.[6,7]
In conclusion the improvements in dyspnea, quality of life and
exacerbations with tiotropium have been consistently demonstrated [6,7]
whereas these outcomes with salmeterol are either absent or inconsistent
at best.
References
(1) Brusasco V, Hodder R, Miravitlles M, Korducki L, Towse L, Kesten S. Health outcomes following treatment for six months with once daily
tiotropium compared with twice daily salmeterol in patients with COPD. Thorax 2003;58:399-404 .
(2) Mahler DA, Wire P, Horstman D, Chang CN, Yates J, Fischer T, Shah T.
Effectiveness of fluticasone propionate and salmeterol combination
delivered via the Diskus device in the treatment of chronic obstructive
pulmonary disease. Am J Resp Crit Care Med 2002;166:1084-1091.
(3) Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvid A, Anderson
J, Maden C. Combined salmeterol and fluticasone in the treatment of
chronic obstructive pulmonary disease: a randomized controlled trial.
Lancet 2003;361:449-456.
(4) Rennard SI, Anderson W, ZuWallack R, Broughton J, Bailey W, Friedman M,
Wisniewski M, Rickard K. Use of a long-acting inhaled B2-adrenergic
agonist, salmeterol xinfoate in patients with chronic obstructive
pulmonary disease. Am J Resp Crit Care Med2001;163:1087-92.
(5) Chapman KR, Arvidsson P, Chuchalin AG, Dhillon DP, Faurschou P,
Goldstein RS, Kuipers AF. The addition of salmeterol 50 mcg bid to
anticholinergic treatment in patients with COPD: a randomized placebo
controlled trial. Can Respir J 2002;9:178-185.
(6) Casaburi R, Mahler DA, Jones PW, Wanner A, San Pedro G, ZuWallack RL,
Menjoge SS, Serby CW, Witek TJ. A long-term evaluation of once-daily
inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J
2002;19(2):217-24.
(7) Vincken W, van Noord JA, Greefhorst APM, Bantje ThA, Kesten S, Korducki
L, Cornelissen PJG. Improved health outcomes in patients with COPD during
1 yr’s treatment with tiotropium. Eur Respir J 2002;19(2):209-16.
I would be grateful if the PE Guidelines Development Committee could
clarify the validity of the pre-test probability (PTP) score which was
quoted in the 1997 guidelines for PE and which reappears in the latest PE
guidelines.
In the 1997 guidelines it clearly states that the suggested
PTP score had not been validated, but was derived from the works of others
in particular Wells in Canada. Howe...
I would be grateful if the PE Guidelines Development Committee could
clarify the validity of the pre-test probability (PTP) score which was
quoted in the 1997 guidelines for PE and which reappears in the latest PE
guidelines.
In the 1997 guidelines it clearly states that the suggested
PTP score had not been validated, but was derived from the works of others
in particular Wells in Canada. However, although the latest guideline
still refers to the simple PTP from 1997, none of the quoted references
supporting its use in this National guideline, have formally validated the
criteria. As so much emphasis is placed on the low or intermediate PTP
score, combined with the D-Dimer result, in many cases excluding patients
from further tests for PE, I wonder if we should be recommending a PTP
score which has not been validated in an unselected cohort of patients
with suspected or possible PE.
Dear Editor,
As Professor Treasure observed in his editorial written in the BMJ this week pneumonectomy for cancer still has a postoperative mortality of 10% to 15% despite patients being rejected if their respiratory function is limited.
Patients who cannot climb stairs before a pneumonectomy had "similar morbidity rates (31.1 vs. 35.6%, respectively, P=0.7), but higher mortality rates (15.6 vs. 4....
Dear Editor
Dr Leckridge[1] is correct to state that the children in the study had mild to moderate symptoms of asthma at the time of recruitment. Children with more severe symptoms were excluded at the request of the Ethics Committee, because of the risks that could arise if they stopped their conventional medication. Our study tested homeopathy as an adjunct to standard medical management, not an alternative.
...Dear Editor,
Lung cancer accounts for 1 in 3 cancer deaths and 25% of cancer registrations. Recognition that accurate and prompt diagnosis can help save lives has led to the formation of the multidisciplinary team (MDT), which consists primarily of chest physicians, thoracic surgeons, radiologists, pathologists, and oncologists, in the management of patients with lung cancer.
A study was conducted to assess the...
Dear Editor
One of the paradoxes of modern medicine is the rapid growing incidence of immune-based diseases over the last half of the century.
Despite enormous advances in our understanding of the immune system, and our ability to manipulate immunity in experienced animals and man, we have not been able to curtail these diseases. In fact, it is becoming increasing evident that immune hypersensitivity response...
Dear Editor,
Dr Toma and colleagues [1] describe interesting directions along which fibreoptic bronchoscopy may develop. The authors quite rightly state that rigid bronchoscopy has largely fallen within the domain of thoracic surgeons. Furthermore the techniques available until relatively recently were limited. I think it appropriate to ask the question “will this situation change”? In my opinion it already has...
Dear Editor
With great interest, we read the guidelines for the management of suspected acute pulmonary embolism (PE) by the British Thoracic Society (June issue 2003).[1] In the discussion of treatment options, the guidelines state that surgical embolectomy should only be considered in cases with absolute contraindications to thrombolysis, which is rarely an important consideration in a life-threatening situat...
Dear Editor,
Re: Symptoms and the early diagnosis of lung cancer
Five year survival of patients with Lung Cancer in the United Kingdom is disappointing and the comparisons made by Birring et al. [1] and others with some internationally published data have been consistently unfavourable [2]. Doctors and government bodies in the United Kingdom have searched for differences in patients, disease or treatmen...
Dear Editor
We would like to comment on strength of conclusions of the recent publication by Dr Brusasco et al,[1] particularly that no consideration is given to how the results compare to the balance of evidence that exists.
The paper’s conclusions imply superior efficacy of tiotropium over salmeterol in patients with COPD by emphasising endpoints in which tiotropium shows a difference compar...
Dear Editor
In his letter, Dr Devoy is questioning the strength of the conclusion in our publication regarding the clinical efficacy of salmeterol on dyspnea, quality of life and reductions of exacerbations. We had stated that the effects with long-acting ß2-adrenergic bronchodilators on COPD exacerbations and on other health outcomes has provided inconsistent results [1] We note that Dr Devoy’s argument is mo...
Dear Editor
I would be grateful if the PE Guidelines Development Committee could clarify the validity of the pre-test probability (PTP) score which was quoted in the 1997 guidelines for PE and which reappears in the latest PE guidelines.
In the 1997 guidelines it clearly states that the suggested PTP score had not been validated, but was derived from the works of others in particular Wells in Canada. Howe...
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