Title: Extracorporeal CO2 removal (ECCO2R) in patients with stable COPD with chronic hypercapnia: applying the concept.
Pradipta Bhakta, Antonio M. Esquinas, Brian O’Brien.
Authors:
1. Dr. Pradipta Bhakta (MD, MNAMS, FCAI, EDRA, EDIC)
Consultant,
Department of Anaesthesia and Intensive Care,
University Hospital Kerry, Tralee, Kerry, Ireland.
Phone: 00353894137596.
Email: bhaktadr@hotmail.com
2. Dr. Antonio M. Esquinas (PhD, MD)
Consultant,
Department of Intensive Care,
Hospital Morales Meseguer,
Murcia, Spain.
Phone: 0034609321966
Email: antmesquinas@gmail.com
3. Dr. Brian O’Brien [FCARCSI, FJFICMI, FCICM (ANZ)]
Consultant and Chair,
Department of Anaesthesia and Intensive Care,
Cork University Hospital, Cork, Ireland.
Mobile: 00353877931656
Email: drbobrien@hotmail.com
Authors and their role:
1. Dr. Pradipta Bhakta: Was involved analysis of the article, writing and editing the letter.
2. Dr. Antonio M. Esquinas: Was involved analysis of the article, writing and editing the letter.
3. Dr. Brian O’Brien: Was involved analysis of the article, writing and editing the letter.
Corresponding Author: Dr. Pradipta Bhakta,
Consultant,
Departm...
Title: Extracorporeal CO2 removal (ECCO2R) in patients with stable COPD with chronic hypercapnia: applying the concept.
Pradipta Bhakta, Antonio M. Esquinas, Brian O’Brien.
Authors:
1. Dr. Pradipta Bhakta (MD, MNAMS, FCAI, EDRA, EDIC)
Consultant,
Department of Anaesthesia and Intensive Care,
University Hospital Kerry, Tralee, Kerry, Ireland.
Phone: 00353894137596.
Email: bhaktadr@hotmail.com
2. Dr. Antonio M. Esquinas (PhD, MD)
Consultant,
Department of Intensive Care,
Hospital Morales Meseguer,
Murcia, Spain.
Phone: 0034609321966
Email: antmesquinas@gmail.com
3. Dr. Brian O’Brien [FCARCSI, FJFICMI, FCICM (ANZ)]
Consultant and Chair,
Department of Anaesthesia and Intensive Care,
Cork University Hospital, Cork, Ireland.
Mobile: 00353877931656
Email: drbobrien@hotmail.com
Authors and their role:
1. Dr. Pradipta Bhakta: Was involved analysis of the article, writing and editing the letter.
2. Dr. Antonio M. Esquinas: Was involved analysis of the article, writing and editing the letter.
3. Dr. Brian O’Brien: Was involved analysis of the article, writing and editing the letter.
Corresponding Author: Dr. Pradipta Bhakta,
Consultant,
Department of Anaesthesia and Intensive Care,
University Hospital Kerry, Tralee, Kerry, Ireland.
Phone: 00353894137596
Email: bhaktadr@hotmail.com
Category of the article: Correspondence in response to article by Pisani L et al.
Running Title: Letter replying to Pisani L et al.
Financial support: No funding other than personal was used in conducting the audit as well as writing the manuscript. We declare that we have no financial and/or personal relationships with other people or organizations that could inappropriately influence (bias) our work.
Conflict of Interest: The authors report no conflicts of interest.
Ethical Approval: Not applicable.
Word Count: 500.
Figure no: 0.
Table No: 0.
To The Editor,
We read with interest the proof-of-concept by Pisani and colleagues and congratulate them on this important work.1 We believe that several methodological details warrant analysis to facilitate extrapolation of their findings into the clinical context.
In particular, it appears the authors characterise non-invasive ventilation (NIV) entirely as a mode of carbon dioxide (CO2) removal. We would emphasize its value as a modality to improve oxygenation. Many patients with chronic obstructive pulmonary disease (COPD) are hypoxic in part because of alveolar displacement of oxygen by expired CO2.2 The consequent type 2 respiratory failure, characteristic of advanced COPD with alveolar hypoventilation, by definition incorporates accompanying hypoxia.3 In evaluating the efficacy of ECCO2R in such patients, they only concentrated on the hypercapnic rather than the hypoxic aspect. NIV however offers both benefits.4 In selecting hypercapnic patients who have failed NIV therapy for the ECCO2R group, we would suggest that in such severe cases symptomatic relief and long-term CO2 reduction cannot occur without improved oxygenation. Effectively oxygen (O2) replaces CO2 eliminated from the alveoli, haemoglobin and cells. But if this aspect is ignored, the use of ECCO2R for 24 hours cannot contribute in the longer term. If we have understood correctly, in the ECCO2R rather than use additional O2, air flow was used to eliminate CO2. Patients in the ECCO2R group, having failed NIV trials in the preceding 6 months, were spontaneously breathing room air. This raises the question of how they were able to tolerate this. In this context we also wonder if the cases were matched for disease severity. Is it possible that milder cases were included, perhaps who were intolerant of NIV due to claustrophobia, discomfort or asynchrony? These points might be clarified further.
A second broad point we would raise is the acceptance of normalized pH in chronic COPD patients with chronic acid-base disturbances, which are typically compensated by the kidney and by buffers in the circulation.5 We agree that in patients with severely diseased functional lung tissue the elimination of CO2 can provide temporary improvement in the arterial blood gas values, but wonder how the authors might speculate on future innovations to extend or capitalise on these benefits.
Thirdly, while studying severe cases of COPD, the study included patients with pH levels above 7.35 while their PaCO2 exceeded 50 mmHg. There is no value given for HCO3 which is clearly important. Ideally full data might be provided to allow categorisation as per the GOLD staging classification.6
Fourthly, in highlighting the role of ECCO2R in severe COPD patients, they have emphasised the failure of NIV. It ought to be observed that ECCO2R has similarly failed to benefit patients with acute respiratory distress syndrome.7 In severe cases of COPD, CO2 load is not the sole mediator of improved outcomes nor of symptomatic benefit, although it is a major issue with multiple adverse effects.3 We would welcome the authors’ views on these points and their thoughts on how their findings may become relevant to clinical practice in the future.
Pradipta Bhakta,
Antonio M. Esquinas,
Brian O’Brien.
References
1. Pisani L, Nava S, Desiderio E, Polverino M, Tonetti T, Ranieri VM. Extracorporeal CO2 removal (ECCO2R) in patients with stable COPD with chronic hypercapnia: a proof-of-concept study [published online ahead of print, 2020 Aug 5]. Thorax. 2020;thoraxjnl-2020-214744. doi:10.1136/thoraxjnl-2020-214744.
2. Kent BD, Mitchell PD, McNicholas WT. Hypoxemia in patients with COPD: cause, effects, and disease progression. Int J Chron Obstruct Pulmon Dis. 2011;6:199-208.
3. Agustí A, Hogg JC. Update on the Pathogenesis of Chronic Obstructive Pulmonary Disease. N Engl J Med. 2019;381(13):1248-1256.
4. Coleman JM 3rd, Wolfe LF, Kalhan R. Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2019;16(9):1091-1098.
5. Bruno CM, Valenti M. Acid-base disorders in patients with chronic obstructive pulmonary disease: a pathophysiological review. J Biomed Biotechnol. 2012;2012:915150.
6. Singh D, Agusti A, Anzueto A, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019;53(5):1900164.
7. Fitzgerald M, Millar J, Blackwood B, et al. Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review. Crit Care. 2014;18(3):222.
The sneeze is depicted as horizontal, presumably for the camera. In a real sneeze, the head first tends to first tilt back, but during the actual sneeze, tends to point downwards. This means that large droplets tend to move toward the floor. Would have been nice to see a P2/N95 mask. Apart from that, a useful paper.
Caretto et al’s brief communication[1] shines some additional light on an unresolved question of the role of alpha-1 antitrypsin deficiency (AATD) screening in patients with bronchiectasis. The authors conclude that testing of an unselected UK population (presumably with a primary diagnosis of bronchiectasis) identifies severe AATD in less than 1% of cases and that routine screening does not significantly impact on clinical management. Whilst these conclusions may be broadly applicable, it may be advisable to qualify the recommendation with some further detail to avoid potential misinterpretation and the consequent complete avoidance of AATD testing in patients with bronchiectasis.
The study rationale originates from apparent conflicting recommendations of guidelines for bronchiectasis[2] and those for AATD[3]. It is stated by the authors that the latter advises AATD testing in all cases of bronchiectasis, whereas the guidelines (in recommendation 1c) in fact advocate testing in cases of ‘unexplained’ bronchiectasis. The use of the term ‘unexplained’ implies the use of a staged approach to the investigation of bronchiectasis with AATD testing reserved for a selected bronchiectasis population in which a diagnosis remains elusive despite clinically appropriate initial investigations.
Studies of bronchiectasis in AATD are few in number and relatively small in size. Nevertheless, there is some consistency in the findings. In their conclusions from a study of t...
Caretto et al’s brief communication[1] shines some additional light on an unresolved question of the role of alpha-1 antitrypsin deficiency (AATD) screening in patients with bronchiectasis. The authors conclude that testing of an unselected UK population (presumably with a primary diagnosis of bronchiectasis) identifies severe AATD in less than 1% of cases and that routine screening does not significantly impact on clinical management. Whilst these conclusions may be broadly applicable, it may be advisable to qualify the recommendation with some further detail to avoid potential misinterpretation and the consequent complete avoidance of AATD testing in patients with bronchiectasis.
The study rationale originates from apparent conflicting recommendations of guidelines for bronchiectasis[2] and those for AATD[3]. It is stated by the authors that the latter advises AATD testing in all cases of bronchiectasis, whereas the guidelines (in recommendation 1c) in fact advocate testing in cases of ‘unexplained’ bronchiectasis. The use of the term ‘unexplained’ implies the use of a staged approach to the investigation of bronchiectasis with AATD testing reserved for a selected bronchiectasis population in which a diagnosis remains elusive despite clinically appropriate initial investigations.
Studies of bronchiectasis in AATD are few in number and relatively small in size. Nevertheless, there is some consistency in the findings. In their conclusions from a study of the distribution of AATD alleles in an unselected bronchiectasis population, the presence of bronchiectasis in PiZ patients was considered by Cuvelier et al[4] to be a consequence of emphysema rather than a primary effect. This association had been previously suggested by small case series[5,6] and, in our subsequent study of 74 individuals with the PiZ phenotype, we were able to demonstrate using quantitative CT imaging that there is a clear association between the severity of emphysema and the severity of bronchiectasis, and a tendency for co-location of the two pathologies[7] (comparable associations between emphysema and bronchiectasis are also seen in patients with non-deficient or usual COPD). Whilst this relationship held true for the majority of our study population, we identified a sub-group of 6 patients in whom the bronchiectasis was of the greatest severity but with a relative paucity of emphysema. This sub-group also included the only 3 patients with cystic bronchiectasis. Our interpretation of these findings was that the sub-group was representative of a distinct clinical phenotype, possibly with individuals who had an alternative underlying cause for their bronchiectasis, perhaps amplified by AATD. On the basis of our results, screening for AATD in patients who have bronchiectasis alone will likely not identify patients with severe AATD and other causes should first be sought. In the absence of any other cause, testing for AATD should then be considered. Testing for AATD in patients with bronchiectasis and co-existing emphysema, particularly when basal and panlobular in nature, should be undertaken according to the advice on testing for AATD in COPD guidelines for the investigation of patients with emphysema.
It would, therefore, seem that AATD testing in patients with bronchiectasis would be best reserved for patients with unexplained bronchiectasis in whom initial investigations have failed to identify a cause, and particularly in patients with co-existing emphysema. Whether the bronchiectasis in such patients would respond positively to AAT augmentation therapy remains unknown but, since bronchiectatic change is relatively common in AATD patients with emphysema, review of sequential scans in those who are or have been taking part in the placebo-controlled trials of augmentation with a focus on sequential bronchiectatic changes may prove informative.
References:
1 Caretto L, Morrison M, Donovan J, et al. Utility of routine screening for alpha-1 antitrypsin deficiency in patients with bronchiectasis. Thorax 2020; 75:592-593.
2 Hill AT, Sullivan AL, Chalmers JD, et al. British thoracic Society guideline for
bronchiectasis in adults. Thorax 2019;74:1–69.
3 Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1
antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis 2016;3:668–82.
4 Cuvelier A, Muir JF, Hellot MF, et al. Distribution of alpha(1)-antitrypsin alleles in patients with bronchiectasis. Chest 2000;117:415–9.
5 Guest PJ, Hansell DM. High resolution computed tomography (HRCT) in emphysema associated with alpha-1 antitrypsin deficiency. Clin Radiol 1992; 45:260–266
6 King MA, Stone JA, Diaz PT, et al. a1-Antitrypsin deficiency: evaluation of bronchiectasis with CT. Radiology 1996; 199:137–141
7 Parr DG, Guest PG, Reynolds JH, et al. Prevalence and impact of bronchiectasis in
alpha1-antitrypsin deficiency. Am J Respir Crit Care Med 2007;176:1215–21.
We read with interest the article by Koeckerling et al. (1) regarding ‘Awake Prone
Positioning in COVID’. The authors have discussed the pros and cons of an
intervention that is being widely used during the COVID-19 pandemic. Although
we broadly agree with their assessment, there are some inaccuracies we would
like to point out as well as a few issues where we would like to offer an
alternative viewpoint:
1. Koeckerling and colleagues (1) quote that 78% of patients with severe
ARDS from a study by Ding et al (2) needed intubation. The original study
was performed prior to COVID-19 pandemic and reported that 55% of
patients with moderate to severe ARDS undergoing awake prone
positioning in conjunction with high flow nasal oxygen (HFNO) /non-
invasive ventilation (NIV) avoided intubation. All clinicians would agree that
invasive mechanical ventilation should not be delayed in the face of a
failing non-invasive intervention. The monitoring of the response to any
treatment is key to determining the appropriate management plan.
2. Koeckerling and colleagues report that CT scanning is essential to identify
which patients would benefit from awake prone positioning but this may not
be possible in view of the large numbers of patients. Gattinoni et al. do
describe different phenotypes based on CT appearances, but this is to
explain the pathophysiology of in different ph...
We read with interest the article by Koeckerling et al. (1) regarding ‘Awake Prone
Positioning in COVID’. The authors have discussed the pros and cons of an
intervention that is being widely used during the COVID-19 pandemic. Although
we broadly agree with their assessment, there are some inaccuracies we would
like to point out as well as a few issues where we would like to offer an
alternative viewpoint:
1. Koeckerling and colleagues (1) quote that 78% of patients with severe
ARDS from a study by Ding et al (2) needed intubation. The original study
was performed prior to COVID-19 pandemic and reported that 55% of
patients with moderate to severe ARDS undergoing awake prone
positioning in conjunction with high flow nasal oxygen (HFNO) /non-
invasive ventilation (NIV) avoided intubation. All clinicians would agree that
invasive mechanical ventilation should not be delayed in the face of a
failing non-invasive intervention. The monitoring of the response to any
treatment is key to determining the appropriate management plan.
2. Koeckerling and colleagues report that CT scanning is essential to identify
which patients would benefit from awake prone positioning but this may not
be possible in view of the large numbers of patients. Gattinoni et al. do
describe different phenotypes based on CT appearances, but this is to
explain the pathophysiology of in different phases of acute respiratory
failure due to COVID-19 pneumonia. They and other authors of studies
describing awake prone positioning do not mention CT chest as a pre-
requisite for awake prone positioning. This strategy is based solely on
oxygen requirement. Prone positioning was initiated once patients needed
more than 4 liters/minute or 28% to 40% oxygen and did not meet any
exclusion criteria.
3. Koeckerling and colleagues further suggest that it would be difficult to
maintain awake prone positioning for 12-16 hours, a duration seen to be
essential for survival benefit during mechanical ventilation. Although it is
difficult to tolerate awake prone positioning for long periods, studies have
reported that patients perform several sessions of prone positioning each
day, totaling up to 6 to 12 hours as needed. Patients on mechanical
ventilation tend to have much more advanced ARDS, which may require a
longer duration of prone positioning to get optimal benefit. Patients
undergoing awake prone positioning have earlier and less severe lung
injury and could benefit from a somewhat shorter duration of prone
positioning. This is supported by findings of Coppo et al. (3) demonstrating
better outcome with earlier initiation of prone positioning.
4. Koeckerling and colleagues report that awake prone positioning could
induce cough leading to aerosol generation of virus. Although this is
theoretically possible, there have been no studies that have reported this.
Moreover, when we used this strategy in our own practice, we did not
observe an increased coughing associated with awake prone positioning.
An alternative to awake prone positioning would be use of continuous
positive airway pressure (CPAP) or HFNO which are considered aerosol
generating procedures themselves and we would expect standard
infection, prevention and control measures to be put in place.
5. Koeckerling and colleagues comment that the Intensive Care Society (ICS)
recommends a blanket policy for use of prone positioning. The ICS has
provided a guidance on indications and settings for awake prone
positioning. The guidance does not say that any patients fulfilling the
suitability criteria must undergo awake prone positioning. A number of
societies including the British Thoracic Society, Irish, Italian and German
guidelines recommend the use of CPAP for hypoxaemic respiratory failure
due to COVID-19 with regular monitoring to assess for treatment failure.
Awake prone positioning has been reported to avoid intubation in more
than 50% patients whereas CPAP is associated with a lower success rate
in avoiding invasive mechanical ventilation in COVID pneumonia. (4)
6. As of 5th July 2020 there have been 11,579,892 confirmed cases of
CVOID-19 in 214 countries worldwide with 537173 deaths. This pandemic
has placed a severe strain on ICUs with demand outstripping capacity in
Europe and USA. India is now placed third with 699,402 cases and a rising
death toll. Despite a population of 1·3 billion, India has only 1·9 million
hospital beds, 100,000 Intensive Care Unit (ICU) beds with only 50,000
ventilators that are concentrated in seven (out of 37) states, mostly in the
private sector. (5) Many of the countries which will be most severely
affected by COVID-19 and whose healthcare systems will be overwhelmed
will be in the developing world. We agree with Koeckerling et al. that there
is therefore a powerful argument for the adoption of a simple, inexpensive
strategy in situations of resource limitation.
7. Most data on awake prone positioning is observational and retrospective
with the usual problems inherent in such data. These data therefore need
to be interpreted with caution and a randomised controlled study will be
need to determine the role of awake prone positioning in acute lung injury
in both patients for escalation in a critical care setting and those who are
deemed not for escalation outside the ICU setting (6). A simple
intervention that does not require a CT scan, that can be delivered outside
critical care and could be used in elderly patients who have limits to the
care on offer who are able to lie prone independently could an attractive
intervention in a number of healthcare systems.
References
1. Awake prone positioning in COVID-19. Koeckerling D, Barker J , Mudalige NL, et
al. Thorax 2020. https://thorax.bmj.com/content/thoraxjnl/early/2020/06/15/thoraxjnl-
2020-215133.full.pdf
2. Ding L, Wang L, Ma W, et al. Efficacy and safety of early prone positioning
combined with HFNC or NIV in moderate to severe ARDS: a multi-center
prospective cohort study. Crit Care 2020;24:28.
3.Feasibility and physiological effects of prone positioning in on-intubated
patients with acute respiratory failure due to COVID-19 (PRON-COVID). Coppo
A, Bellani G, Winterton D, et al. Lancet Respir Med 2020
DOI:https://doi.org/10.1016/S2213-2600(20)30268-X
4.COVID-19 in India: State-Wise Estimates of Current Hospital Beds, ICU Beds,
and Ventilators [Internet]. Center for Disease Dynamics, Economics & Policy
5.Severity of respiratory failure and outcome of patients needing a ventilatory
support in the Emergency Department during Italian novel coronavirus SARS-
CoV2 outbreak: Preliminary data on the role of Helmet CPAP and Non-Invasive
Positive Pressure Ventilation. Duca A, Memaj I, Zanardi F et
al. https://doi.org/10.1016/j.eclinm.2020.100419
6.Features of 20133 UK patients in hospital with covid-19 using the ISARIC WHO
Clinical Characterisation Protocol: prospective observational cohort study.
Docherty AB, Harrison EM, GreenCA, et al.
2020;369:m1985 http://dx.doi.org/10.1136/ bmj.m1985
Thank you for inviting us to respond to correspondence from Dr. Andrea Vila, entitled “Active searching for pseudo-asymptomatic contacts during outbreak, as containment measure”.
We would like to establish in greater details what we defined as “asymptomatic” on board our cruise ship. For the first 8 days, prior to the development of fever in the first subject, our 2 ship’s physicians regularly checked for fever in all passengers in a common area, and attended to calls which were predominantly for sea sickness. After day 8, all passengers and crew were seen by one of the two ship’s physicians twice daily, and had body temperature checks. During these visits, symptoms were enquired about. This includes fever, sore throat, cough and myalgias. In mid-March, anosmia was a recognised symptom of Covid-19 infection and was thus included, but dysgeusia and ageusia were not, and thus Vila makes a valid point. However, given that all passengers and crew were seen twice daily between day 8 and day 28, we are confident in the accuracy of the data presented (81% of Covid-19 subjects being asymptomatic), with the above rider. We do not feel that language was a barrier in communication, with the overwhelming number of passengers and crew either having English as their native language, or being fluent in English. In addition one of the ship’s physicians was multilingual.
Vila also accurately states that asymptomatic subjects may be pre-symptomatic. We have follow-up on all p...
Thank you for inviting us to respond to correspondence from Dr. Andrea Vila, entitled “Active searching for pseudo-asymptomatic contacts during outbreak, as containment measure”.
We would like to establish in greater details what we defined as “asymptomatic” on board our cruise ship. For the first 8 days, prior to the development of fever in the first subject, our 2 ship’s physicians regularly checked for fever in all passengers in a common area, and attended to calls which were predominantly for sea sickness. After day 8, all passengers and crew were seen by one of the two ship’s physicians twice daily, and had body temperature checks. During these visits, symptoms were enquired about. This includes fever, sore throat, cough and myalgias. In mid-March, anosmia was a recognised symptom of Covid-19 infection and was thus included, but dysgeusia and ageusia were not, and thus Vila makes a valid point. However, given that all passengers and crew were seen twice daily between day 8 and day 28, we are confident in the accuracy of the data presented (81% of Covid-19 subjects being asymptomatic), with the above rider. We do not feel that language was a barrier in communication, with the overwhelming number of passengers and crew either having English as their native language, or being fluent in English. In addition one of the ship’s physicians was multilingual.
Vila also accurately states that asymptomatic subjects may be pre-symptomatic. We have follow-up on all passengers and crew until day 28, when 116 passengers disembarked and were repatriated. While we are confident our data is accurate till Day 28, we do not at present have complete follow up after Day 28, and do not have a complete dataset as to how many asymptomatic Covid-19 positive subjects went on to develop symptoms after disembarkation. This is the focus of an ongoing research study.
We agree with Vila, that to truly define a subject as asymptomatic, we should include in the questioning and history taking known specific symptoms to help prompt an accurate response. Vila’s list of atypical symptoms will help identify such subjects.
Dear Editor,
Ing and colleagues reported a cruise outbreak in which a high prevalence of asymptomatic SARS-coV-2 infection was noticed. Viral shedding can occur in the absence of symptoms and before symptom onset, and asymptomatic patients represent an epidemiological problem of great public health significance. However, it’s noteworthy that the huge number of asymptomatic patients (81%), contrasts with a high percentage of severe illness (9.4%) reported on the population of the cruise ship. So, there seems to be a gap between asymptomatic and severe cases of COVID-19, with just 9.6% of mild and moderate clinically disease.
Cluster studies conducted in Singapore attributed 6.4% to asymptomatic transmission 1.
Possibly great part of the population of asymptomatic cases, could have been symptomatic but not meeting the ¨case definition¨ at that time, or pre-symptomatic cases (probably the patients had no evaluation after arrival).
Initial case definition has been periodically updated as more knowledge about COVID-19 was available 2, adding mild or atypical symptoms such as diarrhea, constitutional symptoms, sudden onset of anosmia, ageusia or dysgeusia. The latter were recognized in late March and published in April, thus scarcely known at the time of the report 3-5. As of June, it has been reported that up to 83% patients with mild illness develop anosmia (without nasal obstruction) or dysgeusia as an early or initial manifestation in the absence of o...
Dear Editor,
Ing and colleagues reported a cruise outbreak in which a high prevalence of asymptomatic SARS-coV-2 infection was noticed. Viral shedding can occur in the absence of symptoms and before symptom onset, and asymptomatic patients represent an epidemiological problem of great public health significance. However, it’s noteworthy that the huge number of asymptomatic patients (81%), contrasts with a high percentage of severe illness (9.4%) reported on the population of the cruise ship. So, there seems to be a gap between asymptomatic and severe cases of COVID-19, with just 9.6% of mild and moderate clinically disease.
Cluster studies conducted in Singapore attributed 6.4% to asymptomatic transmission 1.
Possibly great part of the population of asymptomatic cases, could have been symptomatic but not meeting the ¨case definition¨ at that time, or pre-symptomatic cases (probably the patients had no evaluation after arrival).
Initial case definition has been periodically updated as more knowledge about COVID-19 was available 2, adding mild or atypical symptoms such as diarrhea, constitutional symptoms, sudden onset of anosmia, ageusia or dysgeusia. The latter were recognized in late March and published in April, thus scarcely known at the time of the report 3-5. As of June, it has been reported that up to 83% patients with mild illness develop anosmia (without nasal obstruction) or dysgeusia as an early or initial manifestation in the absence of other symptoms 3-5. These symptoms may have been challenging for the passengers to describe due to language struggles, thus being unnoticed. In any case, this excellent study provides evidence that many SARS-coV-2 infections are subtle, and perhaps most asymptomatic cases are pseudo-asymptomatic.
Early detection and isolation of COVID-19 patients is an important disease containment strategy; however, the existence of asymptomatic transmission would present
difficult challenges and high risk of unnoticed transmission. Nevertheless, a high index of suspicion, and a broad case definition may allow detection of mild cases that may go unnoticed as asymptomatic, if they are not specifically searched for.
During outbreak studies and contact tracing and testing; special attention is recommended to specifically inquire contacts about atypical symptoms such as anosmia, dysgeusia, diarrhea, conjunctivitis, sore throat, headache and cutaneous manifestations; that may be critical in timely identification of individuals infected with SARS-CoV2 who may be unwittingly transmitting the virus.
Bibliography
1. Wei WE, Li Z, Chiew CJ, Yong SE, Toh MP, Lee VJ. Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020;69:411–415. DOI: http://dx.doi.org/10.15585/mmwr.mm6914e1
2. Tsang, T. K., et al. (2020). "Effect of changing case definitions for COVID-19 on the epidemic curve and transmission parameters in mainland China: a modelling study." Lancet Public Health 5(5): e289-e296.
3. American Academy of Otolaryngology–Head and Neck Surgery https://www.entnet.org/content/aao-hns-anosmia-hyposmia-and-dysgeusia-sy...
4. Eliezer M, Hautefort C, Hamel AL, et al. Sudden and complete olfactory loss function as a possible symptom of COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Apr 8
5. Kaye R, Chang CWD, Kazahaya K, Brereton J, Denneny JC 3rd. COVID-19 Anosmia Reporting Tool: Initial Findings [published online ahead of print, 2020 Apr 28]. Otolaryngol Head Neck Surg. 2020;194599820922992. doi:10.1177/0194599820922992
Dear Editor,
I read with interest Editorial by Wang et al. (1) regarding treatment of asthma in Covid-19 pandemic. It has been reported that allergic diseases, asthma, and chronic obstructive pulmonary disease were not risk factors for SARS-CoV-2 infection as shown in an earlier report from China (2). On the other hand, early data from Centre for Disease Control and Prevention (CDC) in the US suggest a higher rate of asthma in patients hospitalized for severe Covid-19 illness (3). On this background, patients with severe and uncontrolled asthma have also been included to be at increased risk of developing more severe Covid-19 according to CDC (3). It is however unclear whether increased risk is also relevant to the paediatric age group.
I agree with the authors that asthma control on a population scale may have improved due to reduced pollution, the use of face masks, better medication adherence and reduced smoking. However, these factors are of lesser importance in the paediatric age group. There is variability in the use of facial masks in different countries. It is most probably that lesser severe illness of Covid-19 in children due to the disease (asthma and respiratory allergy) itself that is offering some kind of protection. That protection seems to more than that being offered by adherence to medical treatment alone. Results from a recent cohort study indicate that children with asthma and allergies have reduced angiotensin-converting enzyme-2 (ACE2) gen...
Dear Editor,
I read with interest Editorial by Wang et al. (1) regarding treatment of asthma in Covid-19 pandemic. It has been reported that allergic diseases, asthma, and chronic obstructive pulmonary disease were not risk factors for SARS-CoV-2 infection as shown in an earlier report from China (2). On the other hand, early data from Centre for Disease Control and Prevention (CDC) in the US suggest a higher rate of asthma in patients hospitalized for severe Covid-19 illness (3). On this background, patients with severe and uncontrolled asthma have also been included to be at increased risk of developing more severe Covid-19 according to CDC (3). It is however unclear whether increased risk is also relevant to the paediatric age group.
I agree with the authors that asthma control on a population scale may have improved due to reduced pollution, the use of face masks, better medication adherence and reduced smoking. However, these factors are of lesser importance in the paediatric age group. There is variability in the use of facial masks in different countries. It is most probably that lesser severe illness of Covid-19 in children due to the disease (asthma and respiratory allergy) itself that is offering some kind of protection. That protection seems to more than that being offered by adherence to medical treatment alone. Results from a recent cohort study indicate that children with asthma and allergies have reduced angiotensin-converting enzyme-2 (ACE2) gene expression due to down-regulation of the ACE2 receptor (4). In this study, ACE2 expression in respiratory cells was lowest in those with both high levels of allergic sensitization and asthma (4). This might explain why children with asthma and allergic sensitization have apparently less serious illness. At present, reduced ACE2 expression appears to be a potential "protective" mechanism of reduced covid-19 severity in children with asthma and respiratory allergy. Furthermore, in the paediatric age group, cross-immunity from exposure to seasonal coronaviruses is also hypothesized as plausible mechanism for relative mild illness in children (5).
CHANDRA SEKHAR DEVULAPALLI chandev@gmail.com
Chandra Sekhar Devulapalli is M.D., Ph.D., Senior Medical Consultant and Paediatrician, Norwegian Labour and Welfare Administration (NAV), Work and Benefits Kristiania, Oslo, Norway.
References
1) Wang R, Bikov A, Fowler SJ. Treating asthma in the COVID-19 pandemicThorax Published Online First: 10 June 2020. doi: 10.1136/thoraxjnl-2020-215118
2) Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China [published online ahead of print, 2020 Feb 19]. Allergy. 2020;10.1111/all.14238. doi:10.1111/all.14238
3) Centers for Disease Control and Prevention. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020. MMWR. 2020;69.
4) Jackson DJ, Buses WW, Bacharier LB et al. Association of Respiratory Allergy, Asthma and Expression of the SARS-CoV-2 Receptor, ACE2. Journal of Allergy and Clinical Immunology (2020). https://doi.org/10.1016/j.jaci.2020.04.009
5) Devulapalli CS. COVID‐19 is milder in children possibly due to cross immunity. Acta Paediatr. 2020 Jun 10:10.1111/apa.15407. doi: 10.1111/apa.15407. Online ahead of print.
Dear Editor,
We agree with Koeckerling et al. that awake prone positioning, if proven beneficial, could provide a simple resource-conserving intervention that improves outcomes in COVID-19, especially in the resource-limited countries where even with mitigation strategies critical care bed demand is modelled to outstrip supply by a factor of 25.1,2
Currently, our knowledge about prone positioning is extrapolated from studies in non-awake, mechanically ventilated patients and so these proposed benefits remain theoretical.3-6
In addition to the various small-scale observational studies mentioned by Koeckerling et al., a recently published observational study of 24 awake COVID-19 patients concluded that awake prone positioning was well tolerated. However, the numbers were too small to confirm or refute any benefit in this population.7 Randomised control trial (RCT) is the gold standard for evidence in awake prone positioning in COVID-19 population. However, RCT will be a very difficult approach for this intervention due to the likelihood of a lack of equipoise amongst clinicians to recruit. Following national guidelines, many departments would implement this intervention as the standard of care. Awake prone positioning also appears to be a safe intervention in awake patients and may slow the respiratory deterioration in selected patients with COVID-19.1
Following the recent Intensive Care Society (ICS) guideline, clinicians within our institution ha...
Dear Editor,
We agree with Koeckerling et al. that awake prone positioning, if proven beneficial, could provide a simple resource-conserving intervention that improves outcomes in COVID-19, especially in the resource-limited countries where even with mitigation strategies critical care bed demand is modelled to outstrip supply by a factor of 25.1,2
Currently, our knowledge about prone positioning is extrapolated from studies in non-awake, mechanically ventilated patients and so these proposed benefits remain theoretical.3-6
In addition to the various small-scale observational studies mentioned by Koeckerling et al., a recently published observational study of 24 awake COVID-19 patients concluded that awake prone positioning was well tolerated. However, the numbers were too small to confirm or refute any benefit in this population.7 Randomised control trial (RCT) is the gold standard for evidence in awake prone positioning in COVID-19 population. However, RCT will be a very difficult approach for this intervention due to the likelihood of a lack of equipoise amongst clinicians to recruit. Following national guidelines, many departments would implement this intervention as the standard of care. Awake prone positioning also appears to be a safe intervention in awake patients and may slow the respiratory deterioration in selected patients with COVID-19.1
Following the recent Intensive Care Society (ICS) guideline, clinicians within our institution have implemented awake prone positioning as a standard of care in suspected or confirmed COVID-19 patients which we expect is not unique. 8
These provide an opportunity to investigate the possible benefit of awake prone positioning using anonymised routinely collected healthcare data to compare outcomes in supine and prone cohorts before and after the implementation of awake prone positioning. We have developed a robust protocol that have been approved by the Health Research Authority for analysis of this data, but our sample is too small. We call for collaboration between sites that have implemented similar guidance to generate robust outcomes from data already in existence but siloed between sites.
Patients included in the study are all awake, inpatients aged >18years with PCR confirmed nasal swabs for COVID-19 and hypoxic respiratory failure requiring hospitalisation.
We propose collecting data on outcome measures, including all-cause mortality, oxygen consumption, the requirement for invasive mechanical ventilation, length of non-invasive ventilation and length of stay. Propensity score matching will be undertaken to allow comparison between supine and prone cohorts based on common participant descriptors such as age, sex, and gender. However, emerging concerns for COVID study design, such as collider bias 9 (where a factor, such as smoking history, associates both with having a COVID-19 test and disease prognosis), present serious challenges for robust research conclusions; thus, while further patient characteristics will be collected (ethnicity, symptom onset, Rockwood frailty score, drug history, blood results including arterial blood gases), final matching factors will be determined as data from the Office of National Statistics allow for a better understanding of potential colliders to avoid inducing a false association.
Differences in O2 consumption and length of stay in hospital by awake prone positioning status will be estimated using multiple linear regression adjusting for propensity score matching (PSM). Power analyses suggest that with a total sample size of 600 patients (300 supine and 300 prone) we have 80% power to estimate a difference in O2 consumption of at least 20%, a plausible effect size given prior literature.
Risk of all-cause mortality will be estimated using multiple logistic regression adjusting for PSM. With 600 patients, as described above, we will have 80% power to estimate an odds ratio of at least 1.6 or a 60% difference in risk of dying from any cause.
Now is the time to collect pragmatic, reliable evidence about the safety and efficacy of awake prone positioning in COVID-19, so that we may overcome the COVID-19 pandemic in resource-limited settings and will be better prepared for future pandemic peaks.
If you think you can help, please contact raha.west@nhs.net where we will take you through the process and acknowledge your involvement on this worthwhile endeavour.
References
1. Koeckerling D, Barker J, Mudalige NL, et al Awake prone positioning in COVID-19 Thorax Published Online First: 16 June 2020. doi: 10.1136/thoraxjnl-2020-215133
2. https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-...
3. Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. New England Journal of Medicine. 2013;368(23):2159-2168. doi:10.1056/NEJMoa1214103
4. Munshi L, del Sorbo L, Adhikari NKJ, et al. Prone position for acute respiratory distress syndrome: A systematic review and meta-analysis. Annals of the American Thoracic Society. 2017;14(February):S280-S288. doi:10.1513/AnnalsATS.201704-343OT
5. Bloomfield R, Noble DW, Sudlow A. Prone position for acute respiratory failure in adults. Cochrane Database of Systematic Reviews. 2015;2015(11):CD008095. doi:10.1002/14651858.CD008095.pub2
6. Sud S, Friedrich JO, Adhikari NKJ, et al. Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: A systematic review and meta-analysis. CMAJ. 2014;186(10):E381-90. doi:10.1503/cmaj.140081
7. Elharrar X, Trigui Y, Dols A, et al. Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure. JAMA. Published online May 15, 2020. doi:10.1001/jama.2020.8255
8. Bamford P, Bentley A, Dean J, Whitmore D, Wilson -Baig N. ICS Guidance for Prone Positioning of the Conscious COVID Patient 2020
9. Theoretical Motivation for Considering Collider Bias. Using AscRtain. (2020). Retrieved 17 June 2020, from http://apps.mrcieu.ac.uk/ascrtain/
For patients with chronic obstructive pulmonary disease, pulmonary rehabilitation (PR) has demonstrated improvements in physiological measures(1), patient-reported outcomes(2), and health economic indices(3). There is also a growing body of evidence around improvements in frailty(4) sedentary behaviour(5) and social-connectedness(6). The clinical need for alternative delivery modes of programmes, such as pulmonary tele-rehabilitation (PTR) has been clearly established in the COVID-19 pandemic, whereby conventional face-to-face programme provision seems an unlikely reality for the foreseeable future. The rapid remodelling of health services as a result of COVID-19 provides an exciting opportunity to reflect about the traditional aims, structure, outcomes and components of conventional PR programmes. Hansen et al(7) in a recent issue of Thorax provide an excellent, concise literature review, in combination with outcomes from their study, which suggest that PTR is certainly no worse than conventional PR for commonly reported patient outcomes and could indeed offer some benefits in terms of programme completion. However, there are limitations which we believe should be highlighted further.
Hansen et al(7) recruited patients who fulfilled the ‘real world’ inclusion criteria for hospital-based PR. The authors suggest that this may explain why neither study group achieved minimal clinically important difference (MCID) in outcomes. However, patients with similar functiona...
For patients with chronic obstructive pulmonary disease, pulmonary rehabilitation (PR) has demonstrated improvements in physiological measures(1), patient-reported outcomes(2), and health economic indices(3). There is also a growing body of evidence around improvements in frailty(4) sedentary behaviour(5) and social-connectedness(6). The clinical need for alternative delivery modes of programmes, such as pulmonary tele-rehabilitation (PTR) has been clearly established in the COVID-19 pandemic, whereby conventional face-to-face programme provision seems an unlikely reality for the foreseeable future. The rapid remodelling of health services as a result of COVID-19 provides an exciting opportunity to reflect about the traditional aims, structure, outcomes and components of conventional PR programmes. Hansen et al(7) in a recent issue of Thorax provide an excellent, concise literature review, in combination with outcomes from their study, which suggest that PTR is certainly no worse than conventional PR for commonly reported patient outcomes and could indeed offer some benefits in terms of programme completion. However, there are limitations which we believe should be highlighted further.
Hansen et al(7) recruited patients who fulfilled the ‘real world’ inclusion criteria for hospital-based PR. The authors suggest that this may explain why neither study group achieved minimal clinically important difference (MCID) in outcomes. However, patients with similar functional disability and low walking distances included in UK national PR audits(8) did achieve MCIDs and therefore their assumption and external validity of their findings should be questioned. The research hypothesis that PTR would show superiority in 6MWT improvement compared to conventional PR was not demonstrated. The robust blinding procedure used within the study may have reduced any inflated gains that may have otherwise been seen in such trials with limited assessor and this approach should be commended. However, we also believe that the lack of significant difference in walking distance between groups may have also been due to limitations in the method of delivery of the exercise component which was not aligned across both models of programme. Those patients randomised to PTR may not have had a fair chance to show superiority according to the 6MWT primary outcome measure. For example, in comparison to the conventional PR group, the PTR warm-up period was shorter, with no walking component. The PTR group exercised for 35 minutes three times weekly (105 min per week) compared to the conventional PR group who exercised for 60 minutes twice weekly (120 min per week). The primary outcome measure is a walking test, but the intervention does not specifically focus on walking, whereas walking is clearly repeated for the control group. It would be interesting to know the rationale for the decision to make the delivery methods different between groups. More information is required about physical activity guidance given to the PTR group as no practical exercises were reported next to this specific education session in the appendix, compared to practical exercise given in the PR group programme. The course of the 6mwt test was only 20m rather than 30m, which may have limited the distance covered and improved upon for both groups because of a greater frequency of turning. Indeed, in the NETT emphysema trial(9) from which the MCID for 6MWT was referenced for this article(10), participants walked approximately 40 metres further than those in the current PTR trial, despite having lower FEV1% predicted.
We believe that PTR warrants further research and should be simultaneously trialed in an iterative fashion within clinical services given the current need. It is important for this research to use appropriate outcome measures, and interventions matched to the clinical evidence-based PR programmes which are used. This pragmatic approach is required to enable the PR community to grapple with the challenges of this new mode of delivery while providing patients with a rehabilitation option in the COVID-19 era.
References
1. Zatloukal J, Ward S, Houchen-Wolloff L, Harvey-Dunstan T, Singh S. The minimal important difference for the endurance shuttle walk test in individuals with chronic obstructive pulmonary disease following a course of pulmonary rehabilitation. Chronic Respiratory Disease. 2019;16.
2. Nolan CM, Longworth L, Lord J, Canavan JL, Jones SE, Kon SSC, et al. The EQ-5D-5L health status questionnaire in COPD: validity, responsiveness and minimum important difference. Thorax. 2016;71:493-500.
3. Griffiths TL, Phillips CJ, Davies S, Burr ML, Campbell IA. Cost effectiveness of an outpatient multidisciplinary pulmonary rehabilitation programme. Thorax. 2001;56:779-84.
4. Maddocks M, Kon SSC, Canavan JL, Jones SE, Nolan CM, Labey A, et al. Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study. Thorax. 2016;7(11):988-95.
5. Geidl W, Carl J, Cassar S, Lehbert N, Mino E, Wittmann M, et al. Physical Activity and Sedentary Behaviour Patterns in 326 Persons with COPD before Starting a Pulmonary Rehabilitation: A Cluster Analysis. Journal of Clinical Medicine. 2019;8(9):1346.
6. Bu F, Philip K, Fancourt D. Social isolation and loneliness as risk factors for hospital admissions for respiratory disease among older adults. Thorax. 2020.
7. Hansen H, Bieler T, Beyer N, Kallemose T, Wilcke JT, Ostergaard LM, et al. Supervised pulmonary tele-rehabilitation versus pulmonary rehabilitation in severe COPD: a randomised multicentre trial. Thorax. 2020;75(5):413-21.
8. Steiner M, McMillan V, Lowe D, Holzhauer-Barrie J, Mortier K, Riordan J, et al. Pulmonary rehabilitation: An exercise in improvement. National Chronic Obstructive Pulmonary Disease (COPD) Audit Programme: Clinical and organisational audits of pulmonary rehabilitation services in England and Wales 2017. London: RCP; 2018.
9. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348(21):2059-73.
10. Puhan MA, Chandra D, Mosenifar Z, Ries A, Make B, Hansel NN, et al. The minimal important difference of exercise tests in severe COPD. Eur Respir J. 2011;37(4):784-90.
“The Yentl Syndrome” coined in 1991 by Bernadine Healy is the different course of action that the treating physicians usually follow for women than for men (1,2). The name is taken from the 1983 film Yentl starring Barbra Streisand in which her character plays the role of a male in order to attend school and study the Talmud. Being "just like a man" has historically been a price women have had to pay for equality. Throughout the centuries women, considered different and second-class from men, have too often been treated less than equally in various aspects of life, including education and health care (2). Bernadine Healy (1) pointed out in an editorial for the two studies (3,4) published in the same journal demonstrating that women who are hospitalized for coronary heart disease undergo fewer major diagnostic and therapeutic procedures than men as physicians pursue a less aggressive management approach in women than in men, despite greater cardiac disability in women.
Later, two studies (5,6) demonstrate under-treatment of women with medication, including lower rates of aspirin and ACE inhibitor use in stable women compared with men, as well lower rates of ACE inhibitor, beta-blocker and statin medication in acute coronary syndrome women compared with men. Both studies also show gender differences in use of procedures, where stable women undergo more repeat angiography, whereas acute coronary syndrome women undergo fewer angiograms, percutaneous coronary in...
“The Yentl Syndrome” coined in 1991 by Bernadine Healy is the different course of action that the treating physicians usually follow for women than for men (1,2). The name is taken from the 1983 film Yentl starring Barbra Streisand in which her character plays the role of a male in order to attend school and study the Talmud. Being "just like a man" has historically been a price women have had to pay for equality. Throughout the centuries women, considered different and second-class from men, have too often been treated less than equally in various aspects of life, including education and health care (2). Bernadine Healy (1) pointed out in an editorial for the two studies (3,4) published in the same journal demonstrating that women who are hospitalized for coronary heart disease undergo fewer major diagnostic and therapeutic procedures than men as physicians pursue a less aggressive management approach in women than in men, despite greater cardiac disability in women.
Later, two studies (5,6) demonstrate under-treatment of women with medication, including lower rates of aspirin and ACE inhibitor use in stable women compared with men, as well lower rates of ACE inhibitor, beta-blocker and statin medication in acute coronary syndrome women compared with men. Both studies also show gender differences in use of procedures, where stable women undergo more repeat angiography, whereas acute coronary syndrome women undergo fewer angiograms, percutaneous coronary interventions and coronary artery bypass graft procedures compared with their male counterparts.
Prevalence data for childhood asthma in Switzerland suggest a substantial underdiagnosis which seems to be more pronounced in girls (7). Furthermore, women aged 46 to 60 years had less than half the chance of receiving a transplant when compared with men of the same age and race (8).
Recently, it has been reported (9) that patient gender influences diagnosis of idiopathic pulmonary fibrosis (IPF). Sixty clinical cases collected from a single centre, were scored by 404 physicians from 76 countries for a total of 24240 physician-case evaluations. Using clinical information, physicians were asked to provide up to five diagnoses, together with their diagnostic confidence.
A diagnosis of IPF was made significantly more frequently in male patients compared with female (37.8% vs 10.6%; p<0.0001), and with greater mean diagnostic confidence (p<0.001). The odds of a male patient receiving an IPF diagnosis was greater than that of female patients, after adjusting for confounders (OR=3.05, 95% CI: 2.81 to 3.31), especially if the scan was not definite for the usual interstitial pneumonia (UIP) pattern. This was true whether IPF was listed as a first choice or second-choice diagnosis. The first-choice diagnosis of IPF was made in 37.8% of male patients and 10.6% of female patients. In contrast, female patients more frequently received a first-choice diagnosis of connective tissue disease related interstitial lung disease (CTD-ILD) (p<0.001) or of hypersensitivity pneumonitis (p<0.001).
Mortality was higher in women (HR=2.21, 95% CI: 2.02 to 2.41) than in men (HR=1.26, 95% CI: 1.20 to 1.33), suggesting that men were more often misclassified as having IPF. This difference in mortality was especially pronounced when the diagnosis of IPF in females was made by the subgroup of physicians who were considered experts in the field (HR=4.16, 95%CI: 3.10 to 5.90).
Actually, this is the first study to actually assess how an international sampling of pneumonologists considers patient gender in their diagnostic impression for IPF, suggesting clinicians place a remarkable emphasis on male gender in their pre-test diagnostic probability of this disease (10, 11). These data suggest that the Yentl syndrome seems to be alive today and may be present in other clinical entities that should be investigated meticulously in further studies.
References
1. Healy B. The Yentl syndrome. N Engl J Med. 1991; 325:274-276.
2. Yentl Syndrome. WIKIPEDIA, retrieved 25 Feb., 2020
3. Ayanian JZ, Epstein AM. Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med 1991;325:221–5.
4. Steingart RM et al. Sex Differences in the Management of Coronary Artery Disease. Survival and Ventricular Enlargement Investigators. N Engl J Med 1991;325:226-30.
5. Johnston N, Schenck-Gustafsson K, Lagerkvist B. Are we using cardiovascular medications and coronary angiography appropriately in men and women with chest pain? Eur Heart J, 2011: 32: 1331-1336
6. Bugiardini R, Yan AT, Yan RT, Fitchett D, Langer A, Manfrini O, Goodman SG. Factors influencing underutilization of evidence-based therapies in women on behalf of the Canadian Acute Coronary Syndrome Registry I and II Investigators, Eur Heart J, 2011; 32:1337-1344
7. Kühni CE, Sennhauser FH. The Yentl syndrome in childhood asthma: Risk factors for undertreatment in Swiss children Pediatric Pulmonology 1995;19956-160
8. Kjellstrand CM. Age, sex, and race inequality in renal transplantation. Arch Intern Med. 1988; 148:1305-1309.
9. Assayag D, Morisset J, Johannson K, Wells AU, Walsh SLF. Patient gender bias on the diagnosis of idiopathic pulmonary fibrosis. Thorax, 2020–213968.
10. Tzilas V, Valeyre D, Tzouvelekis A, Bouros D. Taking a giant step in the diagnosis of idiopathic pulmonary fibrosis. Lancet Respir Med. 2018;6:82-84.
11. Respiratory Diseases in Women. Edited by S. Buist and C.E. Mapp. European Respiratory Society Monographs. 2003, vol. 25.
Title: Extracorporeal CO2 removal (ECCO2R) in patients with stable COPD with chronic hypercapnia: applying the concept.
Show MorePradipta Bhakta, Antonio M. Esquinas, Brian O’Brien.
Authors:
1. Dr. Pradipta Bhakta (MD, MNAMS, FCAI, EDRA, EDIC)
Consultant,
Department of Anaesthesia and Intensive Care,
University Hospital Kerry, Tralee, Kerry, Ireland.
Phone: 00353894137596.
Email: bhaktadr@hotmail.com
2. Dr. Antonio M. Esquinas (PhD, MD)
Consultant,
Department of Intensive Care,
Hospital Morales Meseguer,
Murcia, Spain.
Phone: 0034609321966
Email: antmesquinas@gmail.com
3. Dr. Brian O’Brien [FCARCSI, FJFICMI, FCICM (ANZ)]
Consultant and Chair,
Department of Anaesthesia and Intensive Care,
Cork University Hospital, Cork, Ireland.
Mobile: 00353877931656
Email: drbobrien@hotmail.com
Authors and their role:
1. Dr. Pradipta Bhakta: Was involved analysis of the article, writing and editing the letter.
2. Dr. Antonio M. Esquinas: Was involved analysis of the article, writing and editing the letter.
3. Dr. Brian O’Brien: Was involved analysis of the article, writing and editing the letter.
Corresponding Author: Dr. Pradipta Bhakta,
Consultant,
Departm...
The sneeze is depicted as horizontal, presumably for the camera. In a real sneeze, the head first tends to first tilt back, but during the actual sneeze, tends to point downwards. This means that large droplets tend to move toward the floor. Would have been nice to see a P2/N95 mask. Apart from that, a useful paper.
Caretto et al’s brief communication[1] shines some additional light on an unresolved question of the role of alpha-1 antitrypsin deficiency (AATD) screening in patients with bronchiectasis. The authors conclude that testing of an unselected UK population (presumably with a primary diagnosis of bronchiectasis) identifies severe AATD in less than 1% of cases and that routine screening does not significantly impact on clinical management. Whilst these conclusions may be broadly applicable, it may be advisable to qualify the recommendation with some further detail to avoid potential misinterpretation and the consequent complete avoidance of AATD testing in patients with bronchiectasis.
The study rationale originates from apparent conflicting recommendations of guidelines for bronchiectasis[2] and those for AATD[3]. It is stated by the authors that the latter advises AATD testing in all cases of bronchiectasis, whereas the guidelines (in recommendation 1c) in fact advocate testing in cases of ‘unexplained’ bronchiectasis. The use of the term ‘unexplained’ implies the use of a staged approach to the investigation of bronchiectasis with AATD testing reserved for a selected bronchiectasis population in which a diagnosis remains elusive despite clinically appropriate initial investigations.
Studies of bronchiectasis in AATD are few in number and relatively small in size. Nevertheless, there is some consistency in the findings. In their conclusions from a study of t...
Show MoreWe read with interest the article by Koeckerling et al. (1) regarding ‘Awake Prone
Show MorePositioning in COVID’. The authors have discussed the pros and cons of an
intervention that is being widely used during the COVID-19 pandemic. Although
we broadly agree with their assessment, there are some inaccuracies we would
like to point out as well as a few issues where we would like to offer an
alternative viewpoint:
1. Koeckerling and colleagues (1) quote that 78% of patients with severe
ARDS from a study by Ding et al (2) needed intubation. The original study
was performed prior to COVID-19 pandemic and reported that 55% of
patients with moderate to severe ARDS undergoing awake prone
positioning in conjunction with high flow nasal oxygen (HFNO) /non-
invasive ventilation (NIV) avoided intubation. All clinicians would agree that
invasive mechanical ventilation should not be delayed in the face of a
failing non-invasive intervention. The monitoring of the response to any
treatment is key to determining the appropriate management plan.
2. Koeckerling and colleagues report that CT scanning is essential to identify
which patients would benefit from awake prone positioning but this may not
be possible in view of the large numbers of patients. Gattinoni et al. do
describe different phenotypes based on CT appearances, but this is to
explain the pathophysiology of in different ph...
Thank you for inviting us to respond to correspondence from Dr. Andrea Vila, entitled “Active searching for pseudo-asymptomatic contacts during outbreak, as containment measure”.
We would like to establish in greater details what we defined as “asymptomatic” on board our cruise ship. For the first 8 days, prior to the development of fever in the first subject, our 2 ship’s physicians regularly checked for fever in all passengers in a common area, and attended to calls which were predominantly for sea sickness. After day 8, all passengers and crew were seen by one of the two ship’s physicians twice daily, and had body temperature checks. During these visits, symptoms were enquired about. This includes fever, sore throat, cough and myalgias. In mid-March, anosmia was a recognised symptom of Covid-19 infection and was thus included, but dysgeusia and ageusia were not, and thus Vila makes a valid point. However, given that all passengers and crew were seen twice daily between day 8 and day 28, we are confident in the accuracy of the data presented (81% of Covid-19 subjects being asymptomatic), with the above rider. We do not feel that language was a barrier in communication, with the overwhelming number of passengers and crew either having English as their native language, or being fluent in English. In addition one of the ship’s physicians was multilingual.
Vila also accurately states that asymptomatic subjects may be pre-symptomatic. We have follow-up on all p...
Show MoreDear Editor,
Show MoreIng and colleagues reported a cruise outbreak in which a high prevalence of asymptomatic SARS-coV-2 infection was noticed. Viral shedding can occur in the absence of symptoms and before symptom onset, and asymptomatic patients represent an epidemiological problem of great public health significance. However, it’s noteworthy that the huge number of asymptomatic patients (81%), contrasts with a high percentage of severe illness (9.4%) reported on the population of the cruise ship. So, there seems to be a gap between asymptomatic and severe cases of COVID-19, with just 9.6% of mild and moderate clinically disease.
Cluster studies conducted in Singapore attributed 6.4% to asymptomatic transmission 1.
Possibly great part of the population of asymptomatic cases, could have been symptomatic but not meeting the ¨case definition¨ at that time, or pre-symptomatic cases (probably the patients had no evaluation after arrival).
Initial case definition has been periodically updated as more knowledge about COVID-19 was available 2, adding mild or atypical symptoms such as diarrhea, constitutional symptoms, sudden onset of anosmia, ageusia or dysgeusia. The latter were recognized in late March and published in April, thus scarcely known at the time of the report 3-5. As of June, it has been reported that up to 83% patients with mild illness develop anosmia (without nasal obstruction) or dysgeusia as an early or initial manifestation in the absence of o...
Dear Editor,
Show MoreI read with interest Editorial by Wang et al. (1) regarding treatment of asthma in Covid-19 pandemic. It has been reported that allergic diseases, asthma, and chronic obstructive pulmonary disease were not risk factors for SARS-CoV-2 infection as shown in an earlier report from China (2). On the other hand, early data from Centre for Disease Control and Prevention (CDC) in the US suggest a higher rate of asthma in patients hospitalized for severe Covid-19 illness (3). On this background, patients with severe and uncontrolled asthma have also been included to be at increased risk of developing more severe Covid-19 according to CDC (3). It is however unclear whether increased risk is also relevant to the paediatric age group.
I agree with the authors that asthma control on a population scale may have improved due to reduced pollution, the use of face masks, better medication adherence and reduced smoking. However, these factors are of lesser importance in the paediatric age group. There is variability in the use of facial masks in different countries. It is most probably that lesser severe illness of Covid-19 in children due to the disease (asthma and respiratory allergy) itself that is offering some kind of protection. That protection seems to more than that being offered by adherence to medical treatment alone. Results from a recent cohort study indicate that children with asthma and allergies have reduced angiotensin-converting enzyme-2 (ACE2) gen...
Dear Editor,
We agree with Koeckerling et al. that awake prone positioning, if proven beneficial, could provide a simple resource-conserving intervention that improves outcomes in COVID-19, especially in the resource-limited countries where even with mitigation strategies critical care bed demand is modelled to outstrip supply by a factor of 25.1,2
Currently, our knowledge about prone positioning is extrapolated from studies in non-awake, mechanically ventilated patients and so these proposed benefits remain theoretical.3-6
In addition to the various small-scale observational studies mentioned by Koeckerling et al., a recently published observational study of 24 awake COVID-19 patients concluded that awake prone positioning was well tolerated. However, the numbers were too small to confirm or refute any benefit in this population.7 Randomised control trial (RCT) is the gold standard for evidence in awake prone positioning in COVID-19 population. However, RCT will be a very difficult approach for this intervention due to the likelihood of a lack of equipoise amongst clinicians to recruit. Following national guidelines, many departments would implement this intervention as the standard of care. Awake prone positioning also appears to be a safe intervention in awake patients and may slow the respiratory deterioration in selected patients with COVID-19.1
Following the recent Intensive Care Society (ICS) guideline, clinicians within our institution ha...
Show MoreFor patients with chronic obstructive pulmonary disease, pulmonary rehabilitation (PR) has demonstrated improvements in physiological measures(1), patient-reported outcomes(2), and health economic indices(3). There is also a growing body of evidence around improvements in frailty(4) sedentary behaviour(5) and social-connectedness(6). The clinical need for alternative delivery modes of programmes, such as pulmonary tele-rehabilitation (PTR) has been clearly established in the COVID-19 pandemic, whereby conventional face-to-face programme provision seems an unlikely reality for the foreseeable future. The rapid remodelling of health services as a result of COVID-19 provides an exciting opportunity to reflect about the traditional aims, structure, outcomes and components of conventional PR programmes. Hansen et al(7) in a recent issue of Thorax provide an excellent, concise literature review, in combination with outcomes from their study, which suggest that PTR is certainly no worse than conventional PR for commonly reported patient outcomes and could indeed offer some benefits in terms of programme completion. However, there are limitations which we believe should be highlighted further.
Hansen et al(7) recruited patients who fulfilled the ‘real world’ inclusion criteria for hospital-based PR. The authors suggest that this may explain why neither study group achieved minimal clinically important difference (MCID) in outcomes. However, patients with similar functiona...
Show More“The Yentl Syndrome” coined in 1991 by Bernadine Healy is the different course of action that the treating physicians usually follow for women than for men (1,2). The name is taken from the 1983 film Yentl starring Barbra Streisand in which her character plays the role of a male in order to attend school and study the Talmud. Being "just like a man" has historically been a price women have had to pay for equality. Throughout the centuries women, considered different and second-class from men, have too often been treated less than equally in various aspects of life, including education and health care (2). Bernadine Healy (1) pointed out in an editorial for the two studies (3,4) published in the same journal demonstrating that women who are hospitalized for coronary heart disease undergo fewer major diagnostic and therapeutic procedures than men as physicians pursue a less aggressive management approach in women than in men, despite greater cardiac disability in women.
Show MoreLater, two studies (5,6) demonstrate under-treatment of women with medication, including lower rates of aspirin and ACE inhibitor use in stable women compared with men, as well lower rates of ACE inhibitor, beta-blocker and statin medication in acute coronary syndrome women compared with men. Both studies also show gender differences in use of procedures, where stable women undergo more repeat angiography, whereas acute coronary syndrome women undergo fewer angiograms, percutaneous coronary in...
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