We thank Dr. Seijger and colleagues for their analysis. These queries are legitimate and most of the answers are in the online repository. Indeed, in order to comply with the guidelines for letters to Thorax (no more than 1000 words and 2 tables / figures), we could not include all our descriptive and univariate analysis.
We agree that the analysis of survival of patients with type 1 myotonic dystrophy is complex. Our results in Figure 1 and Table R1 demonstrated that patients who refused to initiate NIV, or who delayed NIV initiation, had both a more severe respiratory function and a higher risk for severe event (invasive ventilation or death). Independently from determining whether these severe complications were due to the severity of the initial respiratory function, the lack of compliance to treatment or both, we believe that it was important to underline the presence of this triptych, which is not observed with other neuromuscular groups, such as Duchenne muscular dystrophy where the acceptance of NIV increases with the respiratory dysfunction severity.
Our suggestion that failure to adhere to home mechanical ventilation was associated with increased mortality (tracheostomy excluded), was based on a Cox model analysing predictors of 10-year mortality among NIV users (Table 1). The Cox model was used to evaluate death risk ratios associated with NIV adherence category and was adjusted for other risk factors described in the literature. The covariates i...
We thank Dr. Seijger and colleagues for their analysis. These queries are legitimate and most of the answers are in the online repository. Indeed, in order to comply with the guidelines for letters to Thorax (no more than 1000 words and 2 tables / figures), we could not include all our descriptive and univariate analysis.
We agree that the analysis of survival of patients with type 1 myotonic dystrophy is complex. Our results in Figure 1 and Table R1 demonstrated that patients who refused to initiate NIV, or who delayed NIV initiation, had both a more severe respiratory function and a higher risk for severe event (invasive ventilation or death). Independently from determining whether these severe complications were due to the severity of the initial respiratory function, the lack of compliance to treatment or both, we believe that it was important to underline the presence of this triptych, which is not observed with other neuromuscular groups, such as Duchenne muscular dystrophy where the acceptance of NIV increases with the respiratory dysfunction severity.
Our suggestion that failure to adhere to home mechanical ventilation was associated with increased mortality (tracheostomy excluded), was based on a Cox model analysing predictors of 10-year mortality among NIV users (Table 1). The Cox model was used to evaluate death risk ratios associated with NIV adherence category and was adjusted for other risk factors described in the literature. The covariates included were sex, age at NIV introduction, and variables with a p value <0.15 in the univariate analysis identified by progressive selection (also included in the online repository).
In univariate analysis, having a pacemaker was not significantly associated with mortality. All our DM1 patients are systematically explored in a specialised cardiologic ward [1] which belongs to the same reference center for neuromuscular patients as our unit [2]; therefore patients with diagnosed heart conduction disturbances underwent pacemaker placement [3], which limited their risk of death from cardiac causes. Regarding functional status, all patients were walking.
One of the main objectives of ventilatory support is to improve gas exchanges regardless the mechanism (respiratory pump failure or respiratory drive dysfunction), which means the normalization of PaCO2, and to improve the signs and symptoms, which has already been demonstrated by Nugent and al [4]. However, the aim of our study was to identify the long term impact of mechanical ventilation, and not its short-term effectiveness. Our usual follow-up aims to ensure that patients are well ventilated within the first 3 months of treatment initiation. During nighttime, and daytime when required, both ventilator settings and interfaces are adjusted using repeated polygraphies (with transcutaneous PCO2), or polysomnographies [5, 6] when necessary, until patients-ventilator interaction is correct and nocturnal transcutaneous PCO2 improves. Moreover, we also use pharmacological treatments when residual daytime hypersomnolence is due solely to central neurological dysfunction [7, 8], as our specialised sleep laboratory is also certified as a reference centre for daytime sleepiness, where we can objectively evaluate daytime sleepiness and efficiency of different treatments by Multiple Sleep Latency Tests and/or the Maintenance of Wakefulness Tests [9]. NIV and sleep were usually efficient within the first months and were controlled every year [6] when patients accepted to continue mechanical ventilation and to come back. Therefore, it was not our objective to prove the effectiveness of mechanical ventilation in this manuscript, considering that at this stage the most important factor, in our opinion, is the adherence to treatment.
In conclusion, the main limit of this study is that it involved a single-center which limits the generalization of the findings. However, because there is no data in the literature regarding the long term impact of mechanical ventilation on DM1 patients survival, this study could be considered as the first report on which to base larger, multicenter studies as suggested by Dr. Seijger and colleagues.
Reference
[1] Wahbi K, Babuty D, Probst V, Wissocque L, Labombarda F, Porcher R, Bécane HM, Lazarus A, Béhin A, Laforêt P, Stojkovic T, Clementy N, Dussauge AP, Gourraud JB, Pereon Y, Lacour A, Chapon F, Milliez P, Klug D, Eymard B, Duboc D. Incidence and predictors of sudden death, major conduction defects and sustained ventricular tachyarrhythmias in 1388 patients with myotonic dystrophy type 1. Eur Heart J. 2017 Mar 7;38(10):751-758.
[2] Boussaïd G, Wahbi K, Laforet P, Eymard B, Stojkovic T, Behin A, Djillali A,
Orlikowski D, Prigent H, Lofaso F. Genotype and other determinants of respiratory function in myotonic dystrophy type 1. Neuromuscul Disord. 2018 Mar;28(3):222-228.
[3] Wahbi K, Meune C, Porcher R, Bécane HM, Lazarus A, Laforêt P, Stojkovic T, Béhin A, Radvanyi-Hoffmann H, Eymard B, Duboc D. Electrophysiological study with prophylactic pacing and survival in adults with myotonic dystrophy and conduction system disease. JAMA. 2012 Mar 28;307(12):1292-301.
[4] Nugent AM, Smith IE, Shneerson JM. Domiciliary-assisted ventilation in patients with myotonic dystrophy. Chest. 2002 Feb;121(2):459-64.
[5] Nardi J, Prigent H, Garnier B, Lebargy F, Quera-Salva MA, Orlikowski D, Lofaso F. Efficiency of invasive mechanical ventilation during sleep in Duchenne muscular dystrophy. Sleep Med. 2012 Sep;13(8):1056-65.
[6] Annane D, Quera-Salva MA, Lofaso F, Vercken JB, Lesieur O, Fromageot C, Clair B, Gajdos P, Raphael JC. Mechanisms underlying effects of nocturnal ventilation on daytime blood gases in neuromuscular diseases. Eur Respir J. 1999 Jan;13(1):157-62.
[7] Orlikowski D, Chevret S, Quera-Salva MA, Laforêt P, Lofaso F, Verschueren A, Pouget J, Eymard B, Annane D. Modafinil for the treatment of hypersomnia associated with myotonic muscular dystrophy in adults: a multicenter, prospective, randomized, double-blind, placebo-controlled, 4-week trial. Clin Ther. 2009 Aug;31(8):1765-73.
[8] Hilton-Jones D, Bowler M, Lochmueller H, Longman C, Petty R, Roberts M, Rogers M, Turner C, Wilcox D. Modafinil for excessive daytime sleepiness in myotonic dystrophy type 1--the patients' perspective. Neuromuscul Disord. 2012 Jul;22(7):597-603.
[9] Orlikowski D, Chevret S, Quera-Salva MA, Laforêt P, Lofaso F, Verschueren A, Pouget J, Eymard B, Annane D. Modafinil for the treatment of hypersomnia associated with myotonic muscular dystrophy in adults: a multicenter, prospective, randomized, double-blind, placebo-controlled, 4-week trial. Clin Ther. 2009 Aug;31(8):1765-73.
The authors of both the original article and accompanying editorial endorse the diagnosis of lung nodules with shape sensing robotic assisted bronchoscopy (ssRAB) (1,2). Whether or not you agree with the conclusion from this single centre retrospective single arm study that ssRAB has high sensitivity (without a rigid gold standard) and a better safety profile than CT guided biopsy (the data presented does not include the fact that most CT guided biopsy related haemorrhage and pneumothorax are treated conservatively (3)), cost is not discussed. Upfront capital investment is significant, however in a health care setting where “money follows the patient”, it may be offset by downstream revenues. However ssRAB currently necessitates access to general anaesthesia, not only due to the length of procedure and diameter of the equipment but also any guided bronchoscopy modality without assisted ventilation is hampered by parenchymal atelectasis which creates error between preloaded CT imaging and device position (4). Although the prevalence of global access to general anaesthesia (whether in an operating room or endoscopy unit) is unknown, access in nationalised healthcare settings and healthcare in poorer countries already is inadequate as reflected by surgical wait times (5). Cost is not once discussed in the study presented (1) and even in the editorial (2), the only cost consideration discussed is in relation to the price of clinical trials.
Lesson...
The authors of both the original article and accompanying editorial endorse the diagnosis of lung nodules with shape sensing robotic assisted bronchoscopy (ssRAB) (1,2). Whether or not you agree with the conclusion from this single centre retrospective single arm study that ssRAB has high sensitivity (without a rigid gold standard) and a better safety profile than CT guided biopsy (the data presented does not include the fact that most CT guided biopsy related haemorrhage and pneumothorax are treated conservatively (3)), cost is not discussed. Upfront capital investment is significant, however in a health care setting where “money follows the patient”, it may be offset by downstream revenues. However ssRAB currently necessitates access to general anaesthesia, not only due to the length of procedure and diameter of the equipment but also any guided bronchoscopy modality without assisted ventilation is hampered by parenchymal atelectasis which creates error between preloaded CT imaging and device position (4). Although the prevalence of global access to general anaesthesia (whether in an operating room or endoscopy unit) is unknown, access in nationalised healthcare settings and healthcare in poorer countries already is inadequate as reflected by surgical wait times (5). Cost is not once discussed in the study presented (1) and even in the editorial (2), the only cost consideration discussed is in relation to the price of clinical trials.
Lessons can be learned from the fact that linear array endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) and magnetic navigation bronchoscopy technology was approved at the same time (approximately 2008). Unlike current guided bronchoscopy, the fact that EBUS-TBNA could be transitioned from the operating room to endoscopy units under conscious sedation was vital for global uptake. Larger clinical trials need to include cost comparisons between robotic assisted bronchoscopy and CT guided biopsy, nodule resection and current surveillance protocols for diagnosis and treatment before changes in guidelines for nodule management. Development of accurate ssRAB not requiring general anaesthesia and ventilation would overcome many obstacles
References
1. Fernandez-Bussy S, Yu Lee-Mateus A, Barrios-Ruiz A, Valdes-Camacho S, Lin K, Ibrahim MI, et al. Diagnostic performance of shape-sensing robotic-assisted bronchoscopy for pleural-based and fissure-based pulmonary lesions. Thorax [Internet]. 2025 Feb 17 [cited 2025 Apr 11];80(3). Available from: https://pubmed.ncbi.nlm.nih.gov/39837619/
2. Paez R, Maldonado F. Accumulating evidence supports advanced bronchoscopy as a modality of choice for difficult-to-reach peripheral lung nodules, but questions remain. Thorax [Internet]. 2025 Feb 17 [cited 2025 Apr 11];80(3). Available from: https://pubmed.ncbi.nlm.nih.gov/39922708/
3. Rivera MP, Mehta AC, Wahidi MM. Establishing the Diagnosis of Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013 May 1;143(5):e142S-e165S.
4. Srivastava M, ODonoghue K, Sidun A, Jaeger HA, Ferro A, Crowley D, et al. 3D Position Tracking Using On-Chip Magnetic Sensing in Image-Guided Navigation Bronchoscopy. IEEE Trans Biomed Circuits Syst [Internet]. 2024 Oct [cited 2025 Apr 11];18(5):1123–39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/38568765
5. Heiden BT, Eaton DB, Engelhardt KE, Chang SH, Yan Y, Patel MR, et al. Analysis of Delayed Surgical Treatment and Oncologic Outcomes in Clinical Stage I Non-Small Cell Lung Cancer. JAMA Netw Open [Internet]. 2021 May 27 [cited 2025 Apr 11];4(5). Available from: https://pubmed.ncbi.nlm.nih.gov/34042991/
We read with great interest the systematic review by Srivali et al., titled “Corticosteroid Therapy for Treating Acute Exacerbation of Interstitial Lung Diseases: A Systematic Review,” published in Thorax [1].The topic of corticosteroid use in acute exacerbations (AE) of interstitial lung diseases (ILD) is of immense clinical relevance, and we commend the authors for their comprehensive evaluation of the current evidence base. However, we would like to draw attention to several critical limitations of the existing literature that may impact the robustness of the conclusions drawn in this review.
The authors synthesized data from nine retrospective observational studies, encompassing over 18,000 patients. While this large sample size is notable, it is essential to recognize that the heterogeneity across the included studies significantly limits the ability to draw definitive conclusions. The AE definitions, corticosteroid regimens, and grouping criteria varied considerably across studies, precluding a meta-analysis and necessitating a narrative synthesis. This inherent heterogeneity presents a challenge in interpreting the pooled findings.
One of the key findings of the review is that high-dose corticosteroid therapy (>1 mg/kg prednisolone) may be beneficial for non-idiopathic pulmonary fibrosis (IPF) ILD patients experiencing AE. However, this conclusion primarily stems from the study by Jang et al. [2], which included 131 patients, of whom only 57 were no...
We read with great interest the systematic review by Srivali et al., titled “Corticosteroid Therapy for Treating Acute Exacerbation of Interstitial Lung Diseases: A Systematic Review,” published in Thorax [1].The topic of corticosteroid use in acute exacerbations (AE) of interstitial lung diseases (ILD) is of immense clinical relevance, and we commend the authors for their comprehensive evaluation of the current evidence base. However, we would like to draw attention to several critical limitations of the existing literature that may impact the robustness of the conclusions drawn in this review.
The authors synthesized data from nine retrospective observational studies, encompassing over 18,000 patients. While this large sample size is notable, it is essential to recognize that the heterogeneity across the included studies significantly limits the ability to draw definitive conclusions. The AE definitions, corticosteroid regimens, and grouping criteria varied considerably across studies, precluding a meta-analysis and necessitating a narrative synthesis. This inherent heterogeneity presents a challenge in interpreting the pooled findings.
One of the key findings of the review is that high-dose corticosteroid therapy (>1 mg/kg prednisolone) may be beneficial for non-idiopathic pulmonary fibrosis (IPF) ILD patients experiencing AE. However, this conclusion primarily stems from the study by Jang et al. [2], which included 131 patients, of whom only 57 were non-IPF cases. In contrast, the study by Koshy et al. reported a higher mortality risk in non-IPF AE-ILD patients who received corticosteroids at a dose >0.5 mg/kg compared to those who did not receive corticosteroids [3]. This study included 76 non-IPF patients, and while the difference did not reach statistical significance, the trend raises important questions about the variability in corticosteroid response among different subtypes of ILD.
The discrepancy between these findings could be attributed to several factors, including differences in corticosteroid dosing, the underlying mechanisms of ILD in the cohorts studied, or the triggers of AE. For example, the proportion of patients with connective tissue disease-associated ILD (CTD-ILD) versus hypersensitivity pneumonitis (HP) could influence the observed outcomes, as these subtypes have differing immune-mediated pathophysiology. Additionally, the cause of AE (e.g., infection, aspiration, or non-triggered exacerbation) likely plays a critical role in determining the effectiveness of corticosteroid therapy. These factors underscore the complexity of managing AE-ILD and highlight the need for more precise, prospective studies to better elucidate the role of corticosteroids in different ILD subtypes and AE triggers.
Given these limitations, we urge caution in interpreting this review's findings as definitive evidence supporting high-dose corticosteroid therapy in non-IPF AE-ILD. The current evidence base remains fragile, and the variability in study design and patient populations across the included studies warrants further investigation through randomized controlled trials. These trials should aim to stratify patients by ILD subtype and AE trigger to provide more granular insights into the effectiveness of corticosteroid therapy.
In conclusion, while the review by Srivali et al. provides valuable insights into the potential benefits of corticosteroid therapy in AE-ILD, the limitations of the included studies highlight the need for further research to strengthen the evidence base. We appreciate the authors' efforts in addressing this important clinical question and look forward to future studies that will help clarify the optimal management strategies for AE-ILD.
References
1. Srivali N, De Giacomi F, Moua T, et al. Corticosteroid therapy for treating acute exacerbation of interstitial lung diseases: a systematic review. Thorax 2024 doi: 10.1136/thorax-2024-222636 [published Online First: 20241225]
2. Jang HJ, Yong SH, Leem AY, et al. Corticosteroid responsiveness in patients with acute exacerbation of interstitial lung disease admitted to the emergency department. Sci Rep 2021;11(1):5762. doi: 10.1038/s41598-021-85539-1 [published Online First: 20210311]
3. Koshy K, Barnes H, Farrand E, et al. Steroid therapy in acute exacerbation of fibrotic interstitial lung disease. Respirology 2024;29(9):795-802. doi: 10.1111/resp.14763 [published Online First: 20240602]
We read with interest very large dataset of Filipow et al1, the conclusions of which were that paediatric asthma should be managed by symptoms not spirometry. The authors interpret the variability in first second forced expired volume (FEV1) between occasions when asthma is well controlled as evidence that a change in spirometry is not useful in the clinical management of asthma. Their data could also be used to show that symptoms are not accurately reported in the clinic (which is well known), and therefore spirometry should be the gold standard! However, in the 21st century, when we treat asthma with anti-inflammatory therapy, should we not be measuring what we are trying to treat, namely inflammation2? Both in adults3 and children4,5, elevated peripheral blood eosinophil count (BEC) and exhaled nitric oxide (FeNO) are established markers of active, high-risk disease, and we need to be exploring strategies to use them effectively in treatment, so that those with active inflammation (raised BEC and FeNO) get more anti-inflammatory therapy to try to prevent attacks, and those with inactive disease (low biomarkers) can wean anti-inflammatory treatment.
References
1. Filipow N, Turner S, Petsky HL, et al. Variability in forced expiratory volume in 1 s in children with symptomatically well-controlled asthma. Thorax 2024; 79(12): 1145-50.
2. Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases. Lancet (London, England) 2018; 391...
We read with interest very large dataset of Filipow et al1, the conclusions of which were that paediatric asthma should be managed by symptoms not spirometry. The authors interpret the variability in first second forced expired volume (FEV1) between occasions when asthma is well controlled as evidence that a change in spirometry is not useful in the clinical management of asthma. Their data could also be used to show that symptoms are not accurately reported in the clinic (which is well known), and therefore spirometry should be the gold standard! However, in the 21st century, when we treat asthma with anti-inflammatory therapy, should we not be measuring what we are trying to treat, namely inflammation2? Both in adults3 and children4,5, elevated peripheral blood eosinophil count (BEC) and exhaled nitric oxide (FeNO) are established markers of active, high-risk disease, and we need to be exploring strategies to use them effectively in treatment, so that those with active inflammation (raised BEC and FeNO) get more anti-inflammatory therapy to try to prevent attacks, and those with inactive disease (low biomarkers) can wean anti-inflammatory treatment.
References
1. Filipow N, Turner S, Petsky HL, et al. Variability in forced expiratory volume in 1 s in children with symptomatically well-controlled asthma. Thorax 2024; 79(12): 1145-50.
2. Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases. Lancet (London, England) 2018; 391(10118): 350-400.
3. Couillard S, Laugerud A, Jabeen M, et al. Derivation of a prototype asthma attack risk scale centred on blood eosinophils and exhaled nitric oxide. Thorax 2022; 77(2): 199-202.
4. Couillard S, Ducharme FM, Pavord ID. Clinically accessible biomarkers to assess the modifiable risk of asthma/wheezing attacks in toddlers. The Journal of Allergy and Clinical Immunology: In Practice 2023; 11(6): 1984-5.
5. Bacharier LB, Pavord ID, Maspero JF, Jackson DJ, Fiocchi AG, Mao X, Jacob-Nara JA, Deniz Y, Laws E, Mannent LP, Amin N, Akinlade B, Staudinger HW, Lederer DJ, Hardin M. Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma. J Allergy Clin Immunol. 2024;154(1):101-110.
The article states that on average, 114.5 mL of “pure vodka” was administered to the experimental subjects. Without information on the percentage of alcohol by volume of the vodka, it is not possible to know the average number of grams of alcohol given to the subjects in the study.
Would the authors kindly supply the information on the percentage of alcohol by volume of the vodka used in this study?
We read with great interest this latest valuable addition by Zhang et al. to the growing evidence describing lung function trajectories. Although a relatively small cohort, this study has remarkable retention of participants with lung function measurements from the age of 3 to 45 years, bridging the existing gap in the literature between birth cohort and mid-adult life studies. The authors identify ten FEV1 trajectories, notably more than previous studies, by using a best fitting model with an upper limit of twelve trajectories. Trajectories which rise and fall are of interest as potential targets for public health intervention. Whilst the parallel course of most trajectories identified thus far by this and other cohorts do not inspire confidence in modifiability, their 10-class model does reveal additional decline and catch-up groups not identified by a 6-class model in the supplement. This raises the question as to whether there has been an oversimplification in lung function trajectory modelling in previous analyses, which select between just three and six classes[1–4].
Our interest was particularly sparked by data in supplementary figure S8 where individual lung function trajectories are displayed by class, in which FEV1 in the ‘persistently low’ trajectory demonstrated considerable variability. For clinicians, this individual variability is the hallmark of asthma, especially when combined with the strong association of childhood airway hyper-responsiveness. Th...
We read with great interest this latest valuable addition by Zhang et al. to the growing evidence describing lung function trajectories. Although a relatively small cohort, this study has remarkable retention of participants with lung function measurements from the age of 3 to 45 years, bridging the existing gap in the literature between birth cohort and mid-adult life studies. The authors identify ten FEV1 trajectories, notably more than previous studies, by using a best fitting model with an upper limit of twelve trajectories. Trajectories which rise and fall are of interest as potential targets for public health intervention. Whilst the parallel course of most trajectories identified thus far by this and other cohorts do not inspire confidence in modifiability, their 10-class model does reveal additional decline and catch-up groups not identified by a 6-class model in the supplement. This raises the question as to whether there has been an oversimplification in lung function trajectory modelling in previous analyses, which select between just three and six classes[1–4].
Our interest was particularly sparked by data in supplementary figure S8 where individual lung function trajectories are displayed by class, in which FEV1 in the ‘persistently low’ trajectory demonstrated considerable variability. For clinicians, this individual variability is the hallmark of asthma, especially when combined with the strong association of childhood airway hyper-responsiveness. This suggests a potential target for intensification of asthma management in this group and the possibility of inducing a ‘catch-up’ phase.
In summary we commend this paper which we feel highlights the need to clinically phenotype abnormal trajectories more thoroughly. To date lung function trajectory studies have relied on questionnaire-based self-reported diagnoses of asthma and chest infections. We would argue this is insufficient and should be enriched with objectives physiological measures and biomarkers, especially given the clinical difficulty of diagnosing asthma[5]. To introduce meaningful interventions we need the information we would rely on as clinicians: clinical records of respiratory disease and treatment, markers of type 2 inflammation, assessment of small airways involvement, and even thoracic imaging.
1 Belgrave DCM, Granell R, Turner SW, et al. Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies. Lancet Respir Med. 2018;6:526–34.
2 Berry CE, Billheimer D, Jenkins IC, et al. A Distinct Low Lung Function Trajectory from Childhood to the Fourth Decade of Life. Am J Respir Crit Care Med. 2016;194:607–12.
3 Bui DS, Lodge CJ, Burgess JA, et al. Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life. Lancet Respir Med. 2018;6:535–44.
4 Wang G, Hallberg J, Faner R, et al. Plasticity of Individual Lung Function States from Childhood to Adulthood. Am J Respir Crit Care Med. ;207:406–15.
5 Kavanagh J, Jackson DJ, Kent BD. Over- and under-diagnosis in asthma. Breathe. 2019;15:e20–7.
We thank Professors Azuma and Raghu for their excellent suggestions and comments on our paper. Our study demonstrates the importance of pulmonary vascular resistance (PVR) as a prognostic factor in the initial evaluation of patients with interstitial lung disease (ILD) and highlights the greater significance of PVR over mPAP in right heart catheterisation (RHC) (1). We acknowledge that there is generally less emphasis on PVR compared to the more commonly discussed mean pulmonary arterial pressure (mPAP), and it was our intention to address this discrepancy with our study.
It is important to clarify that we do not recommend systematic RHC at initial evaluation of ILD. Historically, our approach was to perform RHC more frequently at diagnosis, but in recent years, we have limited this to cases where pulmonary hypertension (PH) is suspected. We recently reported a system for predicting mPAP > 20mmHg using a Pa/Ao ratio ≥ 0.9, PaO2 < 80 Torr, and DLco percent predicted < 50% in patients with idiopathic pulmonary fibrosis (IPF) (2). We propose using this system to screen patients before undergoing RHC, with assessments of both mPAP and PVR.
As Azuma and colleagues pointed out, exercise tolerance tests, including the 6-minute walk test (6MWT), might help in predicting PH. As patients with PH have significantly worse desaturation and walking distance in the 6MWT, those who show significant desaturation and/or reduced walking distance during 6MWT are likely to...
We thank Professors Azuma and Raghu for their excellent suggestions and comments on our paper. Our study demonstrates the importance of pulmonary vascular resistance (PVR) as a prognostic factor in the initial evaluation of patients with interstitial lung disease (ILD) and highlights the greater significance of PVR over mPAP in right heart catheterisation (RHC) (1). We acknowledge that there is generally less emphasis on PVR compared to the more commonly discussed mean pulmonary arterial pressure (mPAP), and it was our intention to address this discrepancy with our study.
It is important to clarify that we do not recommend systematic RHC at initial evaluation of ILD. Historically, our approach was to perform RHC more frequently at diagnosis, but in recent years, we have limited this to cases where pulmonary hypertension (PH) is suspected. We recently reported a system for predicting mPAP > 20mmHg using a Pa/Ao ratio ≥ 0.9, PaO2 < 80 Torr, and DLco percent predicted < 50% in patients with idiopathic pulmonary fibrosis (IPF) (2). We propose using this system to screen patients before undergoing RHC, with assessments of both mPAP and PVR.
As Azuma and colleagues pointed out, exercise tolerance tests, including the 6-minute walk test (6MWT), might help in predicting PH. As patients with PH have significantly worse desaturation and walking distance in the 6MWT, those who show significant desaturation and/or reduced walking distance during 6MWT are likely to have PH. We agree that there is a need for the development of non-invasive tests that can detect PH and elevated PVR in an earlier stage.
1. Thorax. 2024 Apr 15;79(5):422-429.
2. Furukawa T, et al. Eur Respir J. 2018 Jan 18;51(1):1701311.
" We congratulate Sato et al to have undertaken the retrospective stud(y that surfaces clinical significance of pulmonary vascular resistance (PVR) as a predictor of mortality in patients with newly diagnosed ILD with normal mean MAP – i.e., < 30mmhg at rest ( 1) .
While their obsrervation is interesting , are the authors advocating right heart catheterization(RHC) for patients with new onset ILD upfront at the time of initial evaluation undergoing diagnostic interventions for diagnosis of ILD ?
Indeed, RHC is an invasive procedure, and the potential benefits and risks must be weighed in considering RHC for patients with new onset ILD for prognostication and consideration of possible therapeutic interventions. Are the authors recommending RHC for patients with new onset ILD without clues for pulmonary hypertension ?
Do the authors have additional non invasive clinical variables/data that correlate with PVR > 2 wood units with mean PAP < 20 mmHg- such as decreased DLCO corrected for hemoglobin, oxygen desaturation with walking, extent of interstitial lung abnormalities , specific diagnosis in patients with new onset ILD that can be used to screen patients to undergo RHC ?
Perhaps, a noninvasive method using an exercise test as was used in assessing patient's endurance of exercise in patients with IPF treated with pirfenidone for IPF(2) might be a screening test prior to considering RHC as a routine for patients with new ons...
" We congratulate Sato et al to have undertaken the retrospective stud(y that surfaces clinical significance of pulmonary vascular resistance (PVR) as a predictor of mortality in patients with newly diagnosed ILD with normal mean MAP – i.e., < 30mmhg at rest ( 1) .
While their obsrervation is interesting , are the authors advocating right heart catheterization(RHC) for patients with new onset ILD upfront at the time of initial evaluation undergoing diagnostic interventions for diagnosis of ILD ?
Indeed, RHC is an invasive procedure, and the potential benefits and risks must be weighed in considering RHC for patients with new onset ILD for prognostication and consideration of possible therapeutic interventions. Are the authors recommending RHC for patients with new onset ILD without clues for pulmonary hypertension ?
Do the authors have additional non invasive clinical variables/data that correlate with PVR > 2 wood units with mean PAP < 20 mmHg- such as decreased DLCO corrected for hemoglobin, oxygen desaturation with walking, extent of interstitial lung abnormalities , specific diagnosis in patients with new onset ILD that can be used to screen patients to undergo RHC ?
Perhaps, a noninvasive method using an exercise test as was used in assessing patient's endurance of exercise in patients with IPF treated with pirfenidone for IPF(2) might be a screening test prior to considering RHC as a routine for patients with new onset ILD " .
1. Sato T, et al Thorax 2024
2. Azuma A, et al AJRCCM 2005
Dear editor,
I read with interest the state-of-the-art review article by Shah et al1. on the effects of non-invasive ventilation (NIV) on sleep in chronic hypercapnic respiratory failure. However, I wish to delve deeper into the topic of Continuous Positive Airway Pressure (CPAP) especially in patients with Chronic Obstructive Pulmonary Disease-Obstructive Sleep Apnea (COPD-OSA) overlap syndrome and obesity hypoventilation syndrome (OHS).
COPD-OSA overlap syndrome was first described by Professor Flenley2, which is associated with an increased frequency and severity of COPD exacerbations3, hospitalizations3, and mortality4. Current data indicates that CPAP improves these outcomes5.
Similarly, in OHS, OSA is highly prevalent, affecting an estimated 90% of patients with OHS6. CPAP has been demonstrated to offer similar benefits to NIV6 7 and is recommended as the initial treatment for stable OHS patients8. CPAP therapy enhances outcomes by improving ventilation, reducing air-trapping, enhancing diaphragmatic function, improving hypercapnic response, and decreasing CO2 production resulting from excessive respiratory muscle work9. Given its advantages and cost-effectiveness compared to NIV, CPAP devices should be considered the initial treatment option7 for both disease before NIV.
Reference
1. Shah NM, Steier J, Hart N, Kaltsakas G. Effects of non-invasive ventilation on sleep in chronic hypercapnic respiratory failure. Thorax 2023 doi: 10.1136...
Dear editor,
I read with interest the state-of-the-art review article by Shah et al1. on the effects of non-invasive ventilation (NIV) on sleep in chronic hypercapnic respiratory failure. However, I wish to delve deeper into the topic of Continuous Positive Airway Pressure (CPAP) especially in patients with Chronic Obstructive Pulmonary Disease-Obstructive Sleep Apnea (COPD-OSA) overlap syndrome and obesity hypoventilation syndrome (OHS).
COPD-OSA overlap syndrome was first described by Professor Flenley2, which is associated with an increased frequency and severity of COPD exacerbations3, hospitalizations3, and mortality4. Current data indicates that CPAP improves these outcomes5.
Similarly, in OHS, OSA is highly prevalent, affecting an estimated 90% of patients with OHS6. CPAP has been demonstrated to offer similar benefits to NIV6 7 and is recommended as the initial treatment for stable OHS patients8. CPAP therapy enhances outcomes by improving ventilation, reducing air-trapping, enhancing diaphragmatic function, improving hypercapnic response, and decreasing CO2 production resulting from excessive respiratory muscle work9. Given its advantages and cost-effectiveness compared to NIV, CPAP devices should be considered the initial treatment option7 for both disease before NIV.
Reference
1. Shah NM, Steier J, Hart N, Kaltsakas G. Effects of non-invasive ventilation on sleep in chronic hypercapnic respiratory failure. Thorax 2023 doi: 10.1136/thorax-2023-220035 [published Online First: 20231118]
2. Flenley DC. Sleep in chronic obstructive lung disease. Clin Chest Med 1985;6(4):651-61.
3. Brennan M, McDonnell MJ, Walsh SM, et al. Review of the prevalence, pathogenesis and management of OSA-COPD overlap. Sleep Breath 2022;26(4):1551-60. doi: 10.1007/s11325-021-02540-8 [published Online First: 20220116]
4. Marin JM, Soriano JB, Carrizo SJ, et al. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med 2010;182(3):325-31. doi: 10.1164/rccm.200912-1869OC [published Online First: 20100408]
5. Srivali N, Thongprayoon C, Tangpanithandee S, et al. The use of continuous positive airway pressure in COPD-OSA overlap syndrome: A systematic review. Sleep Med 2023;108:55-60. doi: 10.1016/j.sleep.2023.05.025 [published Online First: 20230608]
6. Masa JF, Corral J, Alonso ML, et al. Efficacy of Different Treatment Alternatives for Obesity Hypoventilation Syndrome. Pickwick Study. Am J Respir Crit Care Med 2015;192(1):86-95. doi: 10.1164/rccm.201410-1900OC
7. Masa JF, Mokhlesi B, Benitez I, et al. Cost-effectiveness of positive airway pressure modalities in obesity hypoventilation syndrome with severe obstructive sleep apnoea. Thorax 2020;75(6):459-67. doi: 10.1136/thoraxjnl-2019-213622 [published Online First: 20200326]
8. Mokhlesi B, Masa JF, Brozek JL, et al. Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2019;200(3):e6-e24. doi: 10.1164/rccm.201905-1071ST
9. McNicholas WT. COPD-OSA Overlap Syndrome: Evolving Evidence Regarding Epidemiology, Clinical Consequences, and Management. Chest 2017;152(6):1318-26. doi: 10.1016/j.chest.2017.04.160 [published Online First: 20170423]
Thank you to the authors for the excellent and very interesting work published.
I would like to ask about the protocol routine follow-up of patients following an acute pulmonary embolus mentioned in the paper: what did this entail, and how did it differ from the protocol implemented as part of the trial?
Secondly, how did the authors select a follow-up telephone at 2 years post acute pulmonary embolus? As is pointed out in the limitations of section of the paper, this could have missed patients with clinically significant CTEPH who did not survive those 2 years. Would an earlier symptom assessment have led to a greater incidence of false positive echocardiograms showing pulmonary hypertension, or would it lead to patients being missed as not enough time would have passed to allow CTEPH to establish?
We thank Dr. Seijger and colleagues for their analysis. These queries are legitimate and most of the answers are in the online repository. Indeed, in order to comply with the guidelines for letters to Thorax (no more than 1000 words and 2 tables / figures), we could not include all our descriptive and univariate analysis.
We agree that the analysis of survival of patients with type 1 myotonic dystrophy is complex. Our results in Figure 1 and Table R1 demonstrated that patients who refused to initiate NIV, or who delayed NIV initiation, had both a more severe respiratory function and a higher risk for severe event (invasive ventilation or death). Independently from determining whether these severe complications were due to the severity of the initial respiratory function, the lack of compliance to treatment or both, we believe that it was important to underline the presence of this triptych, which is not observed with other neuromuscular groups, such as Duchenne muscular dystrophy where the acceptance of NIV increases with the respiratory dysfunction severity.
Our suggestion that failure to adhere to home mechanical ventilation was associated with increased mortality (tracheostomy excluded), was based on a Cox model analysing predictors of 10-year mortality among NIV users (Table 1). The Cox model was used to evaluate death risk ratios associated with NIV adherence category and was adjusted for other risk factors described in the literature. The covariates i...
Show MoreTo the Editor,
The authors of both the original article and accompanying editorial endorse the diagnosis of lung nodules with shape sensing robotic assisted bronchoscopy (ssRAB) (1,2). Whether or not you agree with the conclusion from this single centre retrospective single arm study that ssRAB has high sensitivity (without a rigid gold standard) and a better safety profile than CT guided biopsy (the data presented does not include the fact that most CT guided biopsy related haemorrhage and pneumothorax are treated conservatively (3)), cost is not discussed. Upfront capital investment is significant, however in a health care setting where “money follows the patient”, it may be offset by downstream revenues. However ssRAB currently necessitates access to general anaesthesia, not only due to the length of procedure and diameter of the equipment but also any guided bronchoscopy modality without assisted ventilation is hampered by parenchymal atelectasis which creates error between preloaded CT imaging and device position (4). Although the prevalence of global access to general anaesthesia (whether in an operating room or endoscopy unit) is unknown, access in nationalised healthcare settings and healthcare in poorer countries already is inadequate as reflected by surgical wait times (5). Cost is not once discussed in the study presented (1) and even in the editorial (2), the only cost consideration discussed is in relation to the price of clinical trials.
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We read with great interest the systematic review by Srivali et al., titled “Corticosteroid Therapy for Treating Acute Exacerbation of Interstitial Lung Diseases: A Systematic Review,” published in Thorax [1].The topic of corticosteroid use in acute exacerbations (AE) of interstitial lung diseases (ILD) is of immense clinical relevance, and we commend the authors for their comprehensive evaluation of the current evidence base. However, we would like to draw attention to several critical limitations of the existing literature that may impact the robustness of the conclusions drawn in this review.
The authors synthesized data from nine retrospective observational studies, encompassing over 18,000 patients. While this large sample size is notable, it is essential to recognize that the heterogeneity across the included studies significantly limits the ability to draw definitive conclusions. The AE definitions, corticosteroid regimens, and grouping criteria varied considerably across studies, precluding a meta-analysis and necessitating a narrative synthesis. This inherent heterogeneity presents a challenge in interpreting the pooled findings.
One of the key findings of the review is that high-dose corticosteroid therapy (>1 mg/kg prednisolone) may be beneficial for non-idiopathic pulmonary fibrosis (IPF) ILD patients experiencing AE. However, this conclusion primarily stems from the study by Jang et al. [2], which included 131 patients, of whom only 57 were no...
Show MoreWe read with interest very large dataset of Filipow et al1, the conclusions of which were that paediatric asthma should be managed by symptoms not spirometry. The authors interpret the variability in first second forced expired volume (FEV1) between occasions when asthma is well controlled as evidence that a change in spirometry is not useful in the clinical management of asthma. Their data could also be used to show that symptoms are not accurately reported in the clinic (which is well known), and therefore spirometry should be the gold standard! However, in the 21st century, when we treat asthma with anti-inflammatory therapy, should we not be measuring what we are trying to treat, namely inflammation2? Both in adults3 and children4,5, elevated peripheral blood eosinophil count (BEC) and exhaled nitric oxide (FeNO) are established markers of active, high-risk disease, and we need to be exploring strategies to use them effectively in treatment, so that those with active inflammation (raised BEC and FeNO) get more anti-inflammatory therapy to try to prevent attacks, and those with inactive disease (low biomarkers) can wean anti-inflammatory treatment.
References
1. Filipow N, Turner S, Petsky HL, et al. Variability in forced expiratory volume in 1 s in children with symptomatically well-controlled asthma. Thorax 2024; 79(12): 1145-50.
2. Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases. Lancet (London, England) 2018; 391...
Show MoreThe article states that on average, 114.5 mL of “pure vodka” was administered to the experimental subjects. Without information on the percentage of alcohol by volume of the vodka, it is not possible to know the average number of grams of alcohol given to the subjects in the study.
Would the authors kindly supply the information on the percentage of alcohol by volume of the vodka used in this study?
We read with great interest this latest valuable addition by Zhang et al. to the growing evidence describing lung function trajectories. Although a relatively small cohort, this study has remarkable retention of participants with lung function measurements from the age of 3 to 45 years, bridging the existing gap in the literature between birth cohort and mid-adult life studies. The authors identify ten FEV1 trajectories, notably more than previous studies, by using a best fitting model with an upper limit of twelve trajectories. Trajectories which rise and fall are of interest as potential targets for public health intervention. Whilst the parallel course of most trajectories identified thus far by this and other cohorts do not inspire confidence in modifiability, their 10-class model does reveal additional decline and catch-up groups not identified by a 6-class model in the supplement. This raises the question as to whether there has been an oversimplification in lung function trajectory modelling in previous analyses, which select between just three and six classes[1–4].
Our interest was particularly sparked by data in supplementary figure S8 where individual lung function trajectories are displayed by class, in which FEV1 in the ‘persistently low’ trajectory demonstrated considerable variability. For clinicians, this individual variability is the hallmark of asthma, especially when combined with the strong association of childhood airway hyper-responsiveness. Th...
Show MoreWe thank Professors Azuma and Raghu for their excellent suggestions and comments on our paper. Our study demonstrates the importance of pulmonary vascular resistance (PVR) as a prognostic factor in the initial evaluation of patients with interstitial lung disease (ILD) and highlights the greater significance of PVR over mPAP in right heart catheterisation (RHC) (1). We acknowledge that there is generally less emphasis on PVR compared to the more commonly discussed mean pulmonary arterial pressure (mPAP), and it was our intention to address this discrepancy with our study.
Show MoreIt is important to clarify that we do not recommend systematic RHC at initial evaluation of ILD. Historically, our approach was to perform RHC more frequently at diagnosis, but in recent years, we have limited this to cases where pulmonary hypertension (PH) is suspected. We recently reported a system for predicting mPAP > 20mmHg using a Pa/Ao ratio ≥ 0.9, PaO2 < 80 Torr, and DLco percent predicted < 50% in patients with idiopathic pulmonary fibrosis (IPF) (2). We propose using this system to screen patients before undergoing RHC, with assessments of both mPAP and PVR.
As Azuma and colleagues pointed out, exercise tolerance tests, including the 6-minute walk test (6MWT), might help in predicting PH. As patients with PH have significantly worse desaturation and walking distance in the 6MWT, those who show significant desaturation and/or reduced walking distance during 6MWT are likely to...
" We congratulate Sato et al to have undertaken the retrospective stud(y that surfaces clinical significance of pulmonary vascular resistance (PVR) as a predictor of mortality in patients with newly diagnosed ILD with normal mean MAP – i.e., < 30mmhg at rest ( 1) .
While their obsrervation is interesting , are the authors advocating right heart catheterization(RHC) for patients with new onset ILD upfront at the time of initial evaluation undergoing diagnostic interventions for diagnosis of ILD ?
Indeed, RHC is an invasive procedure, and the potential benefits and risks must be weighed in considering RHC for patients with new onset ILD for prognostication and consideration of possible therapeutic interventions. Are the authors recommending RHC for patients with new onset ILD without clues for pulmonary hypertension ?
Show MoreDo the authors have additional non invasive clinical variables/data that correlate with PVR > 2 wood units with mean PAP < 20 mmHg- such as decreased DLCO corrected for hemoglobin, oxygen desaturation with walking, extent of interstitial lung abnormalities , specific diagnosis in patients with new onset ILD that can be used to screen patients to undergo RHC ?
Perhaps, a noninvasive method using an exercise test as was used in assessing patient's endurance of exercise in patients with IPF treated with pirfenidone for IPF(2) might be a screening test prior to considering RHC as a routine for patients with new ons...
Dear editor,
I read with interest the state-of-the-art review article by Shah et al1. on the effects of non-invasive ventilation (NIV) on sleep in chronic hypercapnic respiratory failure. However, I wish to delve deeper into the topic of Continuous Positive Airway Pressure (CPAP) especially in patients with Chronic Obstructive Pulmonary Disease-Obstructive Sleep Apnea (COPD-OSA) overlap syndrome and obesity hypoventilation syndrome (OHS).
COPD-OSA overlap syndrome was first described by Professor Flenley2, which is associated with an increased frequency and severity of COPD exacerbations3, hospitalizations3, and mortality4. Current data indicates that CPAP improves these outcomes5.
Similarly, in OHS, OSA is highly prevalent, affecting an estimated 90% of patients with OHS6. CPAP has been demonstrated to offer similar benefits to NIV6 7 and is recommended as the initial treatment for stable OHS patients8. CPAP therapy enhances outcomes by improving ventilation, reducing air-trapping, enhancing diaphragmatic function, improving hypercapnic response, and decreasing CO2 production resulting from excessive respiratory muscle work9. Given its advantages and cost-effectiveness compared to NIV, CPAP devices should be considered the initial treatment option7 for both disease before NIV.
Reference
Show More1. Shah NM, Steier J, Hart N, Kaltsakas G. Effects of non-invasive ventilation on sleep in chronic hypercapnic respiratory failure. Thorax 2023 doi: 10.1136...
Thank you to the authors for the excellent and very interesting work published.
I would like to ask about the protocol routine follow-up of patients following an acute pulmonary embolus mentioned in the paper: what did this entail, and how did it differ from the protocol implemented as part of the trial?
Secondly, how did the authors select a follow-up telephone at 2 years post acute pulmonary embolus? As is pointed out in the limitations of section of the paper, this could have missed patients with clinically significant CTEPH who did not survive those 2 years. Would an earlier symptom assessment have led to a greater incidence of false positive echocardiograms showing pulmonary hypertension, or would it lead to patients being missed as not enough time would have passed to allow CTEPH to establish?
Thank you in advance for your clarifications
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