Dr McFadden is putting forward an interpretation of the small non-
significant decrease in asthma episode contacts seen amongst those with
moderate exposure to passive smoking. In our view this is unwise. The
effect could well be due simply to the play of chance. Further we have
shown that non-clinical factors have a dominant influence on visit
frequency and that the frequency of contacts is a poor measu...
Dr McFadden is putting forward an interpretation of the small non-
significant decrease in asthma episode contacts seen amongst those with
moderate exposure to passive smoking. In our view this is unwise. The
effect could well be due simply to the play of chance. Further we have
shown that non-clinical factors have a dominant influence on visit
frequency and that the frequency of contacts is a poor measure of asthma
morbidity. In consequence our study gives no support at all to the idea
that moderate levels of tobacco smoke suppress asthma. We agree that
further research is needed both into the consequences of passive smoking
and also into the determinants of health care utilisation among children
with asthma.
Iain K Crombie, Professor
Linda Irvine, Research Fellow
Department of Epidemiology and Public Health University of Dundee, Dundee DD1 9SY, UK
We agree with Anderson that age and significant co-morbidity might
reduce the chances of getting histology. In the population of our study
the proportion of patients with a clinical diagnosis was 7%. This
proportion varied from almost 3% for patients younger than 65 to 8% for
those aged 65-79 and 22% for those aged 80 or older. In patients younger
than 65 or in those aged 80 or older this proportio...
We agree with Anderson that age and significant co-morbidity might
reduce the chances of getting histology. In the population of our study
the proportion of patients with a clinical diagnosis was 7%. This
proportion varied from almost 3% for patients younger than 65 to 8% for
those aged 65-79 and 22% for those aged 80 or older. In patients younger
than 65 or in those aged 80 or older this proportion did not decrease with
significant co-morbidity. In patients aged 65-79, however, the proportion
of patients with a clinical diagnosis increased from 5% for patients
without co-morbidity to 7% for those with one co-morbid condition, and to
10% for those with at least two co-morbid conditions.
In our study we only included patients with non-small cell lung
cancer. In those with localized disease 3-year survival significantly
decreased with age.
However, the differences in lung cancer survival within Europe cannot
entirely be explained by differences in age distribution. In the EUROCARE
study [1,2] survival rates were standardised to a common age structure.
Furthermore, the rates were adjusted for the age-specific background
mortality to keep to a minimum the effect of age and competing causes of
death on the overall comparisons. In the United Kingdom the proportion of
microscopically verified lung cancer cases was rather low (about 60%) [3].
Therefore, differences in access to diagnostic care might be responsible
for variation in lung cancer survival, rather than differences in age
distribution or the prevalence of co-morbidity. Registration procedures
might also play a role, because we do not dispose on notifications from
death certificates. This problem becomes larger when access to care is
less optimal. The number of chest physicians in the Netherlands was 2 to 3
times as high as in the UK.
References
(1) Janssen-Heijnen ML, Gatta G, Forman D, et al. Variation in survival
of patients with lung cancer in Europe, 1985-1989. EUROCARE Working Group.
Eur J Cancer 1998;34:2191-6.
(2) Sant M, Aareleid T, Berrino F, et al. EUROCARE-3: survival of
cancer patients diagnosed 1990-94-results and commentary. Ann Oncol
2003;14 Suppl 5:V61-V118.
(3) Capocaccia R, Gatta G, Roazzi P, et al. The EUROCARE-3 database:
methodology of data collection, standardisation, quality control and
statistical analysis. Ann Oncol 2003;14 Suppl 5:V14-V27.
We read with interest the recent article by Niimi et al reporting low
levels of exhaled breath condensate (EBC) pH in patients with chronic
cough [1]. We and others have described low EBC pH in association with
airway inflammation in allergic asthma, cystic fibrosis and
COPD [2][3][4]. In these studies there is a relatively close association
between inflammation and low pH which is shown by the furth...
We read with interest the recent article by Niimi et al reporting low
levels of exhaled breath condensate (EBC) pH in patients with chronic
cough [1]. We and others have described low EBC pH in association with
airway inflammation in allergic asthma, cystic fibrosis and
COPD [2][3][4]. In these studies there is a relatively close association
between inflammation and low pH which is shown by the further fall in pH
during exacerbations [2]. However in non-asthmatic chronic cough whilst
there is a low grade inflammation present in some subjects this is much
less than would be required to invoke inflammation as the major cause of
airway acidification.
It is unclear from the description of the assessment protocol how
patients were allotted their individual diagnostic categories. A positive
methacholine challenge test is not infrequently found in patients with
reflux [5] and, even in classical asthma, reflux is a common phenomenon [6].
We would suggest that there has been a significant under diagnosis of
reflux disease in this cohort because of the lack of a structured history,
the non uniform application of investigations and the failure to perform
full oesophageal assessment, particularly manometry. We have shown that
when oesophageal manometry is not performed a significant number of
patients with reflux cough will be missed [7]. Proton pump inhibitors at
conventional doses only temporarily increase the pH of gastric reflux and
do not prevent reflux per se and, unsurprisingly, only improve symptoms in
a proportion of patients with reflux cough. A failure of cough to improve
with proton pump inhibitors does not therefore adequately rule out reflux
cough.
The simplest explanation for the low airway pH observed by Niimi et
al would be that a large proportion of the subjects have laryngopharyngeal
reflux. This would also explain the otherwise surprising finding of
similar EBC pH across the authors’ diagnostic categories.
References
(1) Niimi A, Nguyen LT, Usmani O, Mann B, Chung KF. Reduced pH and
chloride levels in exhaled breath condensate of patients with chronic
cough. Thorax 2004; 59: 608-612.
(2) Ojoo JC, Mulrennan S, Kastelik JA, Morice AH, Redington AE.
Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma
and in cystic fibrosis. Thorax 2004; (In Press)
(3) Kostikas K, Papatheodorou G, Ganas K, Psathakis K, Panagou P,
Loukides S. pH in expired breath condensate of patients with inflammatory
airway diseases. Am J Respir Crit Care Med. 2002; 165: 1364-1370.
(4) Tate S, MacGregor G, Davis M, Innes JA, Greening AP. Airways in
cystic fibrosis are acidified: detection by exhaled breath condensate.
Thorax 2002; 57: 926-929.
(5) Bagnato GF, Gulli S, Giacobbe O, De Pasquale R, Purello DF.
Bronchial hyperresponsiveness in subjects with gastroesophageal reflux.
Respiration 2000; 67: 507-509.
(6) Vincent D, A.M., Leport J, et al. Gastro-oesophageal reflux
prevalence and relationship with bronchial reactivity in asthma. Eur
Respir J 1997; 10: 2255-2259.
(7) Kastelik JA, Redington AE, Aziz I, et al. Abnormal oesophageal
motility in patients with chronic cough. Thorax 2003; 58: 699-702.
in a recent issue of the Journal, Gan WQ et al. published a systematic review
and meta-analysis of 14 reports which confirmed the strong association between
COPD and biological markers of systemic inflammation [1]. In 6 reports, COPD was
diagnosed according to the presence of a FEV1/FVC ratio lower than 0.7. However,
in the remaining 8 studies this measure was not available, and authors assumed
as affecte...
in a recent issue of the Journal, Gan WQ et al. published a systematic review
and meta-analysis of 14 reports which confirmed the strong association between
COPD and biological markers of systemic inflammation [1]. In 6 reports, COPD was
diagnosed according to the presence of a FEV1/FVC ratio lower than 0.7. However,
in the remaining 8 studies this measure was not available, and authors assumed
as affected by COPD all participants in the lowest quartile of FEV1% and, for
one study [2], of FVC%. In these cases, the corresponding highest quartile group
served as control. Since a COPD diagnosis based on the decreased FEV1/FVC ratio
was lacking in 8 reports, the possibility cannot be excluded that a certain
number of patients included in the meta-analysis did not have COPD, but a
restrictive ventilatory defect. This could be particularly true for participants
to the study by Engstrom [2], who were characterized only by a low FVC.
According to the current GOLD guidelines [3], only a FEV1/FVC ratio lower
than 0.7 indicates airflow obstruction, thus allowing a COPD diagnosis. Indeed,
in the absence of particular pulmonary diseases, many subjects show an
homogenous decrease of all dynamic lung volumes (FEV1, FVC, PEF), without any
alteration of FEV1/FVC ratio, and are thus considered as having “impaired lung
function”. The occurrence of respiratory symptoms [4], the systemic inflammation
[2] and the increased risk of cardiovascular disease [5] are the only features
that restrictive subjects share with COPD. In fact, whereas COPD is
characterized by a decrease in BMI and blood lipids, restrictive subjects often
have abdominal obesity, insulin-resistance and other metabolic risk factors [6].
Although we believe that most of the included patients were really affected
by COPD, the possible inclusion of restrictive patients may have altered the
statistical conclusions of the meta-analysis. In addition, the choice of
selecting patients in the lowest quartile of FEV1 or FVC hindered the authors
from confirming the absence of inflammation in mild COPD (GOLD stage I and II),
a finding previously reported by the same group in a study not included in this
meta-analysis [7].
Because the two groups of restrictive and COPD patients have different
features, the generic term ”impaired lung function” should not be used. Future
studies about the role of inflammation and other cardiovascular risk conditions
in respiratory patients, as well as those investigating the outcome of these
subjects, should clearly distinguish restrictive from COPD patients.
References
(1) Gan WQ, Man SFP, Senthilselvan A, Sin DD. Association between chronic
obstructive pulmonary disease and systemic inflammation: a systematic review and
a meta-analysis. Thorax 2004; 59: 574-580
(2) Engstrom G, Lind P, Hedblad B et
al. Lung function and cardiovascular risk. Relationship with
inflammatory-sensitive plasma protein. Circulation 2002; 106: 2555-2560
(3)
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Publication no.
2701. Bethesda, National Institute for Health, 2001 (2004 update).
(4) Mannino
DM, Ford ES, Redd SC. Obstructive and restrictive lung disease and functional
limitation: data from the Third national Health and Nutrition Examination.
Journal of Internal Medicine 2003; 254: 540-547
(5) Hole DJ, Watt GC, Davey-Smith
G et al. Impaired lung function and mortality risk in men and women: findings
from the Renfrew and Paisley prospective population study. BMJ 1996; 313:
711-715
(6) Lawlor DA, Ebrahim S, Davey-Smith G. Associations of measures of lung
function with insulin resistance and type 2 diabetes: findings from the British
Women’s heart and health Study. Diabetologia 2004; 47: 195-203
(7) Sin DD, Man SFP. Why are patients with obstructive pulmonary disease at increased risk of
cardiovascular diseases? The potential role of systemic inflammation in Chronic
Obstructive Pulmonary Disease. Circulation 2003; 107: 1514-1519
We thank Professor Morice and his colleagues for their interest and
for the issues raised vis-a-vis our manuscript.
The main issue raised concerns the possibility that we may have
missed gastrooesophageal disorders such as reflux and dysmotility in our
cohort of chronic cough patients. In our assessment protocol, we state
that we used oesophageal pH measurements in most patients (32 out of 50)...
We thank Professor Morice and his colleagues for their interest and
for the issues raised vis-a-vis our manuscript.
The main issue raised concerns the possibility that we may have
missed gastrooesophageal disorders such as reflux and dysmotility in our
cohort of chronic cough patients. In our assessment protocol, we state
that we used oesophageal pH measurements in most patients (32 out of 50),
together with a trial of proton pump inhibitor. We are pleased to read
from Professor Morice that proton pump inhibitors “only improve symptoms
in a proportion of patients with reflux cough”, when they reported
previously a very excellent 82% therapeutic response in this group treated
with 'proton pump inhibitors, alginates and conventional advice regarding
diet and posture' [1]. We agree entirely that proton pump inhibitors are
not very efficacious in reflux cough. We have not performed oesophageal
manometry and are aware of Professor Morice’s interesting observations.
They also report that patients with abnormal oesophageal manometry respond
to proton pump inhibition, and therefore we would have picked up such
patients with a proton pump inhibitor trial of therapy. However, the
direct link between oesophageal dysmotility and chronic cough still
remains to be established.
We do not believe we have missed reflux as an associated cause of the
cough and therefore do not agree with the explanation that the reduced
exhaled breath condensate pH is a reflection of larngophargeal reflux
throughout the diagnostic categories. Rather, this is likely to be related
to the chronic inflammatory and remodelling process that is present in the
submucosa of chronic cough patients, associated with asthma or non-
asthmatic causes [2, 3, 4]. We must emphasise that we are assuming that
exhaled breath condensate is a reflection of the epithelial surface
liquid, which needs to be confirmed.
References
(1) Kastelik JA, Redington AE, Aziz I, Buckton GK, Smith CM,
Dakkak M
et al. Abnormal oesophageal motility in patients with chronic cough.
Thorax 2003;58:699-702.
(2) Niimi A, Matsumoto H, Minakuchi M, Kitaichi M, Amitani R.
Airway
remodelling in cough-variant asthma. Lancet 2000;356:564-5.
(3) Boulet LP, Milot J, Boutet M, St Georges F, Laviolette M.
Airway
inflammation in non-asthmatic subjects with chronic cough. Am J Respir Crit
Care Med 1994;149:482-9.
(4) Niimi, A., Cosio, B., Oates, T., Nicholson, A., and Chung,
K. F.
Airway inflammation and remodelling in non-asthmatic patients with chronic
cough: comparison with asthmatics. Amer J Resp Crit Care Med 2003; 167:
A353 (Abstract).
The authors wish to thank Fimognari and colleagues for highlighting
the difficult issue of defining chronic obstructive pulmonary disease
(COPD). In most circumstances, a spirometric cutoff is used to define
COPD, but there is no uniform consensus on what that should be and
different expert panels have promulgated different spirometric cutoff
values [1-4]. COPD is a disease characterized by lung inflam...
The authors wish to thank Fimognari and colleagues for highlighting
the difficult issue of defining chronic obstructive pulmonary disease
(COPD). In most circumstances, a spirometric cutoff is used to define
COPD, but there is no uniform consensus on what that should be and
different expert panels have promulgated different spirometric cutoff
values [1-4]. COPD is a disease characterized by lung inflammation and
patient symptoms (most notably dyspnea). Studies have shown that the
relationship between airway inflammation and patient symptoms with forced
expiratory volume in one second (FEV1) is a continuum, and not threshold-
dependent [5,6]. Thus, any attempts to impose FEV1 (or FEV1 to forced
vital capacity, FVC, ratio) limits in defining COPD are bound to be
arbitrary and contentious. Rather than relying on arbitrary cutoffs, for
large population-based studies, it is reasonable (and useful) to compare
the outcome of interest (in this case systemic inflammation) between
extremes of FEV1 (e.g. worst FEV1 quartile to best quartile group). This
method avoids imposing any arbitrary constraints in the definition of COPD
and allows maximal utilization of the data points. However, a potential
limitation of this approach is the possibility of diagnostic
misclassification between restrictive and obstructive lung diseases. To
specifically address this concern, we excluded population-based studies
wherein a FEV1 to FVC ratio was not used to define COPD (Mendall, Dahl,
and Engstrom’s studies [7-9]) and re-analyzed the C-reactive protein (CRP)
and fibrinogen data. Even after the exclusion of these studies, the
standardized mean difference in the CRP level between COPD and control
subjects was 0.68 units (95% confidence interval, CI, 0.38 to 0.98) or
4.85 mg/L (95% CI, 1.92 to 7.78). For the fibrinogen data, the
standardized mean difference between COPD and control subjects was 0.48
units (95% CI, 0.43 to 0.54) or 0.42 g/L (95% CI, 0.00 to 0.84). These
results indicate that the possible contamination of individuals with
restrictive defect in the groups with low FEV1 or FVC did not influence
the overall findings. Finally, we did not include data from one of our
previous reports [10] because the study sample was taken from the same
source population as Mannino and colleague’s study [11], which was
included in the meta-analysis.
Don D. Sin
Wen Qi Gan
S. F. Paul Man
Department of Medicine, University of British Columbia, Vancouver, Canada
Ambikaipakan Senthilselvan.
Department of Public Health Sciences, University of Alberta, Edmonton,
Canada
References
(1) Fabbri LM, Hurd SS; GOLD Scientific Committee. Global Strategy for the
Diagnosis, Management and Prevention of COPD: 2003 update. Eur Respir J.
2003; 22:1-2.
(2) The COPD Guidelines Group of the Standards of Care Committee of
the British Thoracic Society. British Thoracic Society guidelines for the
management of chronic obstructive pulmonary disease. Thorax. 1997;52(suppl
5):S1-S28.
(3) Siafakas NM, Vermeire P, Pride NB, et al. Optimal assessment and
management of chronic obstructive pulmonary disease (COPD). The European
Respiratory Society Task Force. Eur Respir J. 1995;8:1398-420.
(4) American Thoracic Society. Standards for the diagnosis and care
of patients with chronic obstructive pulmonary disease. Am J Respir Crit
Care Med. 1995; 152:S77-S120.
(5) Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway
obstruction in chronic obstructive pulmonary disease. N Engl J Med.
2004;350:2645-53.
(6) Sin DD, Jones RL, Mannino DM, Paul Man SF. Forced expiratory
volume in 1 second and physical activity in the general population. Am J
Med. 2004;117:270-3.
(7) Mendall MA, Strachan DP, Butland BK, et al. C-reactive protein:
relation to total mortality, cardiovascular mortality and cardiovascular
risk factors in men. Eur Heart J 2000;21:1584-90.
(8) Dahl M, Tybjaerg-Hansen A, Vestbo J, et al. Elevated plasma
fibrinogen associated with reduced pulmonary function and increased risk
of chronic obstructive pulmonary disease. Am J Respir Crit Care Med
2001;164:1008-11.
(9) Engstrom G, Lind P, Hedblad B, et al. Lung function and
cardiovascular risk: relationship with inflammation-sensitive plasma
proteins. Circulation 2002;106:2555-60.
(10) Sin DD, Man SF. Why are patients with chronic obstructive
pulmonary disease at increased risk of cardiovascular diseases? The
potential role of systemic inflammation in chronic obstructive pulmonary
disease. Circulation 2003;107:1514-9.
(11) Mannino DM, Ford ES, Redd SC. Obstructive and restrictive lung
disease and markers of inflammation: Data from the third national health
and nutrition examination. Am J Med 2003;114:758-62.
Thank you for a well-reasoned explanation on the effect of yoga on
asthma.
The study quoted [1] which justifies the Buteyko technique was flawed
by:
* unequal groups in that the Buteyko group initially required 1½ times the
steroids of the control group
* the Buteyko group receiving seven times the follow-up phone calls as the
control group, plus extra breathin...
Thank you for a well-reasoned explanation on the effect of yoga on
asthma.
The study quoted [1] which justifies the Buteyko technique was flawed
by:
* unequal groups in that the Buteyko group initially required 1½ times the
steroids of the control group
* the Buteyko group receiving seven times the follow-up phone calls as the
control group, plus extra breathing classes.
Also, no significant difference was found in quality of life scores at the
end of the trial.
However, there is anecdotal evidence of excellent results in some
patients, representing the overlap of hyperventilation syndrome and asthma.[2] If patients with asthma are given the simple Nijmegen questionnaire [3] to identify coexisting hyperventilation syndrome, a chartered
physiotherapist can usually treat them successfully.[4]
References
(1) Bowler SD, Green A, Mitchell CA (1998) Buteyko breathing
techniques in asthma: a randomised controlled trial. Med.J.Aust, 169, 575-8.
(2) Demeter SL (1986) Hyperventilation syndrome and asthma. Am J Med 1986;81:989-94.
(3) Hough A. Physiotherapy in Respiratory Care, 3rd edition. (www.nelsonthornes.com), 2001.
“A good surgeon knows how to operate.
A better surgeon knows when to operate.
The best surgeon knows when not to operate.”
Clinical Surgery in General 3rd Edition
Royal College of Surgeons of England Course Manual
We found the article "Effect of comorbidity on the treatment and
prognosis of elderly patients with non-small cell lung cancer" by Janssen-
Heijnen et al [1] very interesti...
“A good surgeon knows how to operate.
A better surgeon knows when to operate.
The best surgeon knows when not to operate.”
Clinical Surgery in General 3rd Edition
Royal College of Surgeons of England Course Manual
We found the article "Effect of comorbidity on the treatment and
prognosis of elderly patients with non-small cell lung cancer" by Janssen-
Heijnen et al [1] very interesting, as it highlights the increasing clinical
problems health care professionals face within the changing demographics
of an ageing population. The concluding question of “whether the less
aggressive treatment of elderly patients with NSCLC is justified,” is most
thought provoking.
Traditionally, surgeons are keen to perform surgery even on high risk
patients because they have undergone lengthy surgical training, and are
usually itching to put their skills into practice. Furthermore, surgery
may be the only treatment available that offers a realistic chance of cure
for the disease. The decision not to operate on an individual is often
more difficult and painful, as well as requires more experienced clinical
judgement. However, more recently, a whole host of factors including
advances in non-surgical therapies, pressure from clinical performance
auditing and medicolegal litigations may have made decisions not to
operate on elderly patients much easier. Perhaps now the pendulum has
swung too much the other way.
The elderly population of Hong Kong (traditionally defined as 65
years and above) is on the rise from 2.8% in 1961 to 11.1% in 2001, and
such changes are by no means restricted to South East Asia. These patients
have less functional reserve, more associated chronic diseases, and are
more sensitive to anaesthetic agents and medications. There is little
margin, if any for error. In order not to exclude this population from
potential curative surgery, we must become better educated in basic
geriatric principles of care, surgical techniques must be refined, and
perioperative care meticulous. It is the elderly patient group that
minimal access surgery in the form of video-assisted thoracic surgery
(VATS) may confer its greatest benefits. VATS major lung resection is
associated with less access trauma [2] and immunosuppression, [3] better
preserved shoulder function [4] and less post-operative pain [5] as well as
parenteral narcotic requirement [6] compared with open thoracotomy.
Furthermore, post-operative pulmonary function is better preserved
following VATS lung resection. [5] The lowest limits in lung function
parameters that would still be considered acceptable for VATS lobectomy
have not been scientifically studied. [7] Nevertheless, surgeon’s judgement,
experience and technique; the contribution of the excised lobe to overall
lung function; as well as the exact location of the pathology (for
example, upper lobe lesions in patients with bullous emphysema and middle
lobe pathology are favourable candidates for resection) are important
considerations. We have performed lobectomy on a few patients whose FEV1
was less than 1 litre or less than 40% predicted with excellent outcome.[5]
Patients who are not candidates for an anatomical resection could still be
considered for VATS wedge resection.[8] Through these advantages, VATS
allows recruitment of older and sicker patients with multiple
comorbidities who would otherwise not be suitable candidates for lung
resection through a conventional thoracotomy approach.[9,10] A large scale
randomized clinical trial is currently being conducted to confirm this.
Charles Darwin said in the Evolution of the Species, “it is not the
strongest of the species that survives, nor the most intelligent, it is
the one most adaptable to change.” It is our responsibility to improve and
change the way we operate to suit the current times. We must not allow
ourselves to become “extinct” as surgeons, or physicians, in the
management of our patients. More importantly, our elderly patients deserve
the best; advanced age alone in this day and age, should not be a reason
to deny them of a potentially curative operation.
Yours sincerely,
Dr. Calvin S.H. Ng BSc(Hons) MBBS(Hons)(Lond) MRCS(Edin)
Dr. Song Wan MD PhD FRCS(Eng)
Professor Ahmed A. Arifi MD FRCS(CTh)(Edin)
Professor Anthony P.C. Yim MA(cantab) DM(oxon) FRCS(Eng,Glas,Edin) FACS
FCCP
References
(1) Janssen-Heijnen MLG, Smulders S, Lemmens VEPP, Smeenk FWJM, van
Geffen HJAA, Coebergh JWW. Effect of comorbidity on the treatment and
prognosis of elderly patients with non-small cell lung cancer. Thorax
2004;59:602-607
(3) Leaver HA, Craig SR, Yap PL, Walker WS. Lymphocyte responses following
open and minimally invasive thoracic surgery. Eur J Clin Invest
2000;30:230-238
(4) Li WWL, Lee RLM, Lee TW, Ng CSH, Sihoe ADL, Wan IYP, Arifi AA, Yim
APC. The impact of thoracic surgical access on early shoulder function:
video-assisted thoracic surgery versus posterolateral thoracotomy. Eur J
Cardiothorac Surg 2003;23:390-6
(5) Yim APC. VATS major pulmonary resection revisited – controversies,
techniques, and results. Ann Thorac Surg 2002;74:615-23
(6) Yim APC, Wan S, Lee TW, Arifi AA. VATS lobectomy reduces cytokine
responses compared with conventional surgery. Ann Thorac Surg 2000;70:243-
7
(8) Ginsberg RT, Rubinstein LV. Lung Cancer Study Group randomized trial
of lobectomy versus limited resection for T1N0 non-small cell lung cancer.
Ann Thorac Surg 1995;60:615-23
(9) Yim APC. Thoracoscopic surgery in the elderly population. Surg Endosc
1996;10:880-82
(10) Demmy TL, Curtis JJ. Minimally invasive lobectomy directed toward
frail and high-risk patients: a case control study. Ann Thorac Surg
1999;68:194-200
Controversy exists as to the role of modern histamine H1-receptor
antagonists in the treatment of atopic asthma.
Forty-nine patients with atopic asthma were evaluated from three
randomised double-blind placebo-controlled cross-over studies assessing
the anti-inflammatory effects of desloratadine, fexofenadine, and
levocetirizine at clinically recommended doses.
Controversy exists as to the role of modern histamine H1-receptor
antagonists in the treatment of atopic asthma.
Forty-nine patients with atopic asthma were evaluated from three
randomised double-blind placebo-controlled cross-over studies assessing
the anti-inflammatory effects of desloratadine, fexofenadine, and
levocetirizine at clinically recommended doses.
Desloratadine, fexofenadine, and levocetirizine significantly
improved (p <0.05) the provocative concentration of adenosine
monophosphate producing a 20% fall in forced expiratory volume in one
second by 142% compared to placebo. There was a significant improvement (p
<0.05) of 15% in forced expiratory flow at 25% to 75% of maximal lung
volume compared to placebo with desloratadine, fexofenadine, and
levocetirizine. Fexofenadine significantly improved (p <0.05) exhaled
nitric oxide, domiciliary peak expiratory flow, and albuterol rescue use
by 27%, 4%, and 83% respectively compared to placebo. There were no
significant differences in all outcomes among the modern histamine H1-
receptor antagonists.
Modern histamine H1-receptor antagonists improve airway
hyperresponsiveness, small-airways caliber, surrogate inflammatory
markers, and asthma diary outcomes in patients with atopic asthma. Further
studies are required to evaluate the effects of modern histamine H1-
receptor antagonists on asthma exacerbations.
We read with interest McGroder et al’s study on the radiographic findings of patients four months after severe COVID-19 and the associated risk factors. Hürsoy and colleagues’ comment (1) on the paper was equally thought-provoking. We would like to further this discussion by contributing some of our observations from the pulmonology clinic at a major academic medical center in South East Asia.
It has been tremendously challenging globally to achieve precision in the diagnosis of Interstitial Lung Disease (ILD) post-COVID as invasive testing such as lung biopsies are performed sparingly. Histopathological pulmonary findings have largely remained inaccessible since COVID survivors are hypoxic so biopsies pose a high risk for the patient, and healthcare personnels are reluctant to perform such high-risk procedures. Hence, we are left to derive our diagnosis from radiological data and pulmonary function tests (PFTs) of the patient.
We propose that a consensus definition be reached for the diagnosis of post-COVID ILD, one that incorporates well-accepted radiological terms (used to represent any interstitial lung disease). We recommend that lung fibrosis only be classified as ILD if the lung parenchymal abnormalities persist for a minimum of six months after the COVID infection has resolved. Post-COVID ILD should then be further subclassified based on distinct radiological patterns. In our retrospective cohort study, four patterns of post-COV...
We read with interest McGroder et al’s study on the radiographic findings of patients four months after severe COVID-19 and the associated risk factors. Hürsoy and colleagues’ comment (1) on the paper was equally thought-provoking. We would like to further this discussion by contributing some of our observations from the pulmonology clinic at a major academic medical center in South East Asia.
It has been tremendously challenging globally to achieve precision in the diagnosis of Interstitial Lung Disease (ILD) post-COVID as invasive testing such as lung biopsies are performed sparingly. Histopathological pulmonary findings have largely remained inaccessible since COVID survivors are hypoxic so biopsies pose a high risk for the patient, and healthcare personnels are reluctant to perform such high-risk procedures. Hence, we are left to derive our diagnosis from radiological data and pulmonary function tests (PFTs) of the patient.
We propose that a consensus definition be reached for the diagnosis of post-COVID ILD, one that incorporates well-accepted radiological terms (used to represent any interstitial lung disease). We recommend that lung fibrosis only be classified as ILD if the lung parenchymal abnormalities persist for a minimum of six months after the COVID infection has resolved. Post-COVID ILD should then be further subclassified based on distinct radiological patterns. In our retrospective cohort study, four patterns of post-COVID lung parenchymal changes were exhibited by patients with no preexisting lung disease: persistent ground-glass opacities; interlobular septal thickening; reticulation and honeycombing; interlobular septal thickening and reticulations; and patchy consolidation with or without ground-glass opacity (2).
In terms of outcome, within our cohort of severe to critically ill patients, most developed persistent ground-glass opacities or patchy consolidation (with or without ground-glass opacity); a majority of these participants significantly improved (clinically and radiologically) upon administration of corticosteroids (2). Radiological improvement was defined as clearance of at least 50% of lung infiltrates. Reiterating our findings, Han et al. reported ground-glass opacities as the predominant pattern observed in follow-up CT scans of patients with fibrotic-like changes within six months of disease onset (3). Three of the five patients in our study who died had progressive disease with reticulation and honeycombing. To achieve greater accuracy in disease severity assessment and risk stratification, we suggest employing PFTs, particularly to obtain diffusion capacity of the lungs for carbon monoxide (DLCO) and forced vital capacity (FVC) measurements. For the eight out of thirty patients in our cohort who had significant HRCT findings, PFTs were ordered to assess physiological function; three presented with low FVCs (2). In Han et al’s study, abnormal DLCO (less than 80%) at 6-month follow up was a common occurrence in those with fibrotic-like changes (3).
Similar to McGroder et al’s findings, we concluded that the male gender was a significant predisposing factor for post-COVID pulmonary fibrosis. Moreover, like Li et al. and Han et al., we found diabetes mellitus and hypertension to be prevalent comorbidities in patients who developed fibrotic changes (2-4). Interestingly, in our cohort, disease severity did not significantly influence the development of any particular pattern of lung parenchymal abnormality. In light of these observations, we can conclude that the reported lung microstructure changes are not only a ramification of post-ARDS fibrosis or ventilator-induced lung damage but also a consequence of direct virus attack and aberrant local immune response. This is further evidenced by the finding that the Coronavirus induced fibrosis even in moderately ill patients who did not require invasive mechanical ventilation or ICU stay (2).
We hope that prospective studies will further enrich and broaden the global dialogue on post-COVID lung fibrosis.
References:
1. Hürsoy et al. 2021. e-letter https://thorax.bmj.com/eletters
2. Zubairi ABS, Shaikh A, Zubair SM, Ali AS, Awan S, Irfan M. Persistence of post-COVID lung parenchymal abnormalities during the three-month follow-up. Adv Respir Med. 2021;89(5):477–83. Available from: https://pubmed.ncbi.nlm.nih.gov/34612504/
3. Han X, Fan Y, Alwalid O, Li N, Jia X, Yuan M, et al. Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia. Radiology. 2021;299(1):E177-E186.
4. Li Y, Wu J, Wang S, Li X, Zhou J, Huang B, et al. Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan, China. Histopathology. 2021;78(4):542-55.
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Dear Editor,
We read with interest McGroder et al’s study on the radiographic findings of patients four months after severe COVID-19 and the associated risk factors. Hürsoy and colleagues’ comment (1) on the paper was equally thought-provoking. We would like to further this discussion by contributing some of our observations from the pulmonology clinic at a major academic medical center in South East Asia.
It has been tremendously challenging globally to achieve precision in the diagnosis of Interstitial Lung Disease (ILD) post-COVID as invasive testing such as lung biopsies are performed sparingly. Histopathological pulmonary findings have largely remained inaccessible since COVID survivors are hypoxic so biopsies pose a high risk for the patient, and healthcare personnels are reluctant to perform such high-risk procedures. Hence, we are left to derive our diagnosis from radiological data and pulmonary function tests (PFTs) of the patient.
We propose that a consensus definition be reached for the diagnosis of post-COVID ILD, one that incorporates well-accepted radiological terms (used to represent any interstitial lung disease). We recommend that lung fibrosis only be classified as ILD if the lung parenchymal abnormalities persist for a minimum of six months after the COVID infection has resolved. Post-COVID ILD should then be further subclassified based on distinct radiological patterns. In our retrospective cohort study, four patterns of post-COV...
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