Structural Lung Damage Research Articles

Macrophage PD-1 associates with neutrophilia and reduced bacterial killing in early cystic fibrosis airway disease

BackgroundMacrophages are the major resident immune cells in human airways coordinating responses to infection and injury. In cystic fibrosis (CF), neutrophils are recruited to the airways shortly after birth, and actively exocytose damaging enzymes prior to chronic infection, suggesting a potential defect in macrophage immunomodulatory function. Signaling through the exhaustion marker programmed death protein 1 (PD-1) controls macrophage function in cancer, sepsis, and airway infection. Therefore, we sought to identify potential associations between macrophage PD-1 and markers of airway disease in children with CF. MethodsBlood and bronchoalveolar lavage fluid (BALF) were collected from 45 children with CF aged 3 to 62 months and structural lung damage was quantified by computed tomography. The phenotype of airway leukocytes was assessed by flow cytometry, while the release of enzymes and immunomodulatory mediators by molecular assays. ResultsAirway macrophage PD-1 expression correlated positively with structural lung damage, neutrophilic inflammation, and infection. Interestingly, even in the absence of detectable infection, macrophage PD-1 expression was elevated and correlated with neutrophilic inflammation. In an in vitro model mimicking leukocyte recruitment into CF airways, soluble mediators derived from recruited neutrophils directly induced PD-1 expression on recruited monocytes/macrophages, suggesting a causal link between neutrophilic inflammation and macrophage PD-1 expression in CF. Finally, blockade of PD-1 in a short-term culture of CF BALF leukocytes resulted in improved pathogen clearance. ConclusionTaken together, these findings suggest that in early CF lung disease, PD-1 upregulation associates with airway macrophage exhaustion, neutrophil takeover, infection, and structural damage.

T-Cell Defects Associated to Lack of Spike-Specific Antibodies after BNT162b2 Full Immunization Followed by a Booster Dose in Patients with Common Variable Immune Deficiencies.

Following the third booster dose of the mRNA vaccine, Common Variable Immune Deficiencies (CVID) patients may not produce specific antibodies against the virus spike protein. The T-cell abnormalities associated with the absence of antibodies are still a matter of investigation. Spike-specific IgG and IgA, peripheral T cell subsets, CD40L and cytokine expression, and Spike-specific specific T-cells responses were evaluated in 47 CVID and 26 healthy donors after three doses of BNT162b2 vaccine. Testing was performed two weeks after the third vaccine dose. Thirty-six percent of the patients did not produce anti-SARS-CoV-2 IgG or IgA antibodies. Non responder patients had lower peripheral blood lymphocyte counts, circulating naïve and central memory T-cells, low CD40L expression on the CD4+CD45+RO+ and CD8+CD45+RO+ T-cells, high frequencies of TNFα and IFNγ expressing CD8+ T-cells, and defective release of IFNγ and TNFα following stimulation with Spike peptides. Non responders had a more complex disease phenotype, with higher frequencies of structural lung damage and autoimmunity, especially autoimmune cytopenia. Thirty-five percent of them developed a SARS-CoV-2 infection after immunization in comparison to twenty percent of CVID who responded to immunization with antibodies production. CVID-associated T cell abnormalities contributed to the absence of SARS-CoV-2 specific antibodies after full immunization.

Unconventional T Cell Immunity in the Lungs of Young Children with Cystic Fibrosis.

People with Cystic Fibrosis (CF) develop pulmonary inflammation, chronic infection and structural lung damage early in life, with these manifestations being prevalent among preschool children and infants. While early immune events are believed to play critical roles in shaping the progression, severity and disease burden later in life, T cells and their subsets are poorly studied in the CF lung, particularly during the formative early stages of disease. Using flow cytometry, we analyzed Mucosal Associated Invariant T (MAIT) cells, γδ T cells, and Natural Killer T (NKT)-like cells in bronchoalveolar lavage (BAL) samples from seventeen children with CF, aged two to six years old. The effect of age, sex and lung infections on the frequencies of these cells in BAL samples was analysed (grouped data were tested for normality and compared by t-test or Kruskal-Wallis analysis). No difference was noted in the proportions of unconventional T cells related to the sex or age of the children. The frequency of γδ T cells and MAIT cells appeared unchanged by infection status. However, viral infections were associated with a significant increase in the proportion of NKT-like cells. By evaluating T cells in the lungs of children during the early formative stages of CF, this study identified potentially important interactions between these cells and viral pathogens.

Early IL-17A production helps establish Mycobacterium intracellulare infection in mice.

Nontuberculous mycobacteria (NTM) infection is common in patients with structural lung damage. To address how NTM infection is established and causes lung damage, we established an NTM mouse model by intranasal inoculation of clinical isolates of M. intracellulare. During the 39-week course of infection, the bacteria persistently grew in the lung and caused progressive granulomatous and fibrotic lung damage with mortality exceeding 50%. Lung neutrophils were significantly increased at 1 week postinfection, reduced at 2 weeks postinfection and increased again at 39 weeks postinfection. IL-17A was increased in the lungs at 1-2 weeks of infection and reduced at 3 weeks postinfection. Depletion of neutrophils during early (0-2 weeks) and late (32-34 weeks) infection had no effect on mortality or lung damage in chronically infected mice. However, neutralization of IL-17A during early infection significantly reduced bacterial burden, fibrotic lung damage, and mortality in chronically infected mice. Since it is known that IL-17A regulates matrix metalloproteinases (MMPs) and that MMPs contribute to the pathogenesis of pulmonary fibrosis, we determined the levels of MMPs in the lungs of M. intracellulare-infected mice. Interestingly, MMP-3 was significantly reduced by anti-IL-17A neutralizing antibody. Moreover, in vitro data showed that exogenous IL-17A exaggerated the production of MMP-3 by lung epithelial cells upon M. intracellulare infection. Collectively, our findings suggest that early IL-17A production precedes and promotes organized pulmonary M. intracellulare infection in mice, at least in part through MMP-3 production.

Concomitant Pulmonary Tuberculosis and Invasive Aspergillosis Infection in an Immunocompetent Host.

Pulmonary tuberculosis (TB) is a common infection in developing countries and is associated with low socioeconomic status. It is considered a serious infection due it its long-term sequelae. Post-TB lung disease decreases life expectancy and increases the risk of recurrent TB infection. It also significantly increases the risk of other bacterial and fungal infections. Aspergillosis develops in the cavitary lesions of TB, worsening them and resulting in a deteriorating clinical situation. Concomitant pulmonary TB (PTB) and invasive aspergillosis is uncommon, particularly in the absence of factors that suppress the immune system. In this report, we describe the case of a healthy young adult without previous structural lung damage who presented with primary PTB and acute invasive aspergillosis infection, discuss the treatment dilemma and provide a literature review.LEARNING POINTSAspergillosis can mimic tuberculosis (TB) infection.Concomitant pulmonary TB and invasive aspergillosis is uncommon.The co-administration of antifungal and anti-TB medications presents significant therapeutic challenges.

Microbial Community Composition in Explanted Cystic Fibrosis and Control Donor Lungs

To date, investigations of the microbiota in the lungs of people with Cystic Fibrosis (PWCF) have primarily focused on microbial community composition in luminal mucus, with fewer studies observing the microbiota in tissue samples from explanted lung tissue. Here, we analysed both tissue and airway luminal mucus samples extracted from whole explanted lungs of PWCF and unused donor lungs. We determined if the lung microbiota in end-stage CF varied within and between patients, was spatially heterogeneous and related to localized structural damage. Microbial community composition was determined by Illumina MiSeq sequencing and related to the CF-Computed Tomography (CT) score and features of end-stage lung disease on micro-CT. Ninety-eight CF tissue (n=11 patients), 20 CF luminal mucus (n=8 patients) and 33 donor tissue (n=4 patients) samples were analysed. Additionally, we compared 20 paired CF tissue and luminal mucus samples that enabled a direct “geographical” comparison of the microbiota in these two niches. Significant differences in microbial communities were apparent between the 3 groups. However, overlap between the three groups, particularly between CF and donor tissue and CF tissue and CF luminal mucus was also observed. Microbial diversity was lower in CF luminal mucus compared to CF tissue, with dominance higher in luminal mucus. For both CF and donor tissue, intra- and inter-patient variability in ecological parameters was observed. No relationships were observed between ecological parameters and CF-CT score, or features of end-stage lung disease. The end-stage CF lung is characterised by a low diversity microbiota, differing within and between individuals. No clear relationship was observed between regional microbiota variation and structural lung damage.

Longitudinal lung clearance index and association with structural lung damage in children with cystic fibrosis

Longitudinal lung clearance index and association with structural lung damage in children with cystic fibrosis

Chronic airway disease in primary ciliary dyskinesia-spiced with geno-phenotype associations.

Primary ciliary dyskinesia (PCD) can be defined as a multiorgan ciliopathy with a dominant element of chronic airway disease affecting the nose, sinuses, middle ear, and in particular, the lower airways. Although most patients with PCD are diagnosed during preschool years, it is obvious that the chronic lung disease starts its course already from birth. The many faces of the clinical picture change, as does lung function, structural lung damage, the burden of infection, and of treatment throughout life. A markedly severe neutrophil inflammation in the respiratory tract seems pervasive and is only to a minimal extent ameliorated by a treatment strategy, which is predominantly aimed at bacterial infections. An ever‐increasing understanding of the different aspects, their interrelationships, and possible different age courses conditioned by the underlying genotype is the focus of much attention. The future is likely to offer personalized medicine in the form of mRNA therapy, but to that end, it is of utmost importance that all patients with PCD be carefully characterized and given a genetic diagnosis. In this narrative review, we have concentrated on lower airways and summarized the current understanding of the chronic airway disease in this motile ciliopathy. In addition, we highlight the challenges, gaps, and opportunities in PCD lung disease research.

Chest X-rays are less sensitive than multiple breath washout examinations when it comes to detecting early cystic fibrosis lung disease.

AimAnnual chest X‐ray is recommended as routine surveillance to track cystic fibrosis (CF) lung disease. The aim of this study was to investigate the clinical utility of chest X‐rays to track CF lung disease.MethodsChildren at Gothenburg's CF centre who underwent chest X‐rays, multiple breath washouts and chest computed tomography examinations between 1996 and 2016 were included in the study. Chest X‐rays were interpreted with Northern Score (NS). We compared NS to lung clearance index (LCI) and structural lung damage measured by computed tomography using a logistic regression model.ResultsA total of 75 children were included over a median period of 13 years (range: 3.0‐18.0 years). The proportion of children with abnormal NS was significantly lower than the proportion of abnormal LCI up to the age of 4 years (p < 0.05). A normal NS and a normal LCI at age 6 years were associated with a median (10‐90th percentile) total airway disease of 1.8% (0.4‐4.7%) and bronchiectasis of 0.2% (0.0‐1.5%).ConclusionChest X‐rays were less sensitive than multiple breath washout examinations to detect early CF lung disease. The combined results from both methods can be used as an indicator to perform chest computed tomography less frequently.

Aspergillus-related lung disease in people with cystic fibrosis: can imaging help us to diagnose disease?

In people with cystic fibrosis (PwCF), viscous sputum and dysfunction of the mucociliary escalator leads to early and chronic infections. The prevalence of Aspergillus fumigatus in sputum is high in PwCF and the contribution of A. fumigatus to the progression of structural lung disease has been reported. However, overall, relatively little is known about the contribution of A. fumigatus to CF lung disease. More knowledge is needed to aid clinical decisions on whether to start antifungal treatment. In this review, we give an overview of A. fumigatus colonisation and infection in PwCF and the different types of pulmonary disease caused by it. Furthermore, we discuss the current evidence for structural lung damage associated with A. fumigatus in PwCF on chest computed tomography and magnetic resonance imaging. We conclude that radiological outcomes to identify disease caused by A. fumigatus can be important for clinical studies and management.

Risk factors for Pseudomonas aeruginosa airway infection and lung function decline in children with cystic fibrosis

Background Cystic fibrosis (CF) lung disease is characterised by recurrent Pseudomonas aeruginosa (Pa) infections, leading to structural lung damage and decreased survival. The epidemiology of Pa infection and its impact on lung function in people with CF (pwCF), especially in recent birth cohorts, remain uncertain.Methods We included 1,231 French pwCF under 18 years of age. Age at initial acquisition (Pa-IA), chronic colonisation (Pa-CC), and duration from Pa-IA to Pa-CC were estimated using the Kaplan–Meier method. Demographic, clinical, and genetic characteristics were analysed as risk factors for Pa infection using Cox regression models. Lung function decline was assessed by modelling percent-predicted forced expiratory volume in 1 s (ppFEV1) before Pa infection, after Pa-IA, and after Pa-CC.Results Among the 1,231 pwCF, 50% had Pa-IA by the age of 5.1 years [95% confidence interval (CI) 3.8–6.2] and 25% had Pa-CC by the age of 14.7 years (95% CI 12.1 to ∞). We observed that CF-related diabetes and liver disease were risk factors for Pa, while gender, CFTR variants, and CF centre size were not. Genetic variants of TNF, DCTN4, SLC9A3, and CAV2 were confirmed to be associated with Pa. The annual rate of ppFEV1 decline before Pa was -0.38% predicted/year (95% CI -0.59 to -0.18), which decreased significantly after Pa-IA to -0.93% predicted/year (95% CI -1.14 to -0.71) and after Pa-CC to -1.51% predicted/year (95% CI -1.86 to -1.16).Conclusions We identified and replicated several risk factors associated with Pa infection and showed its deleterious impact on lung function in young pwCF. This large-scale study confirmed that Pa airway infection is a major determinant of lung disease severity.

Structural lung disease following allergic bronchopulmonary aspergillosis complicating pediatric cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) complicating cystic fibrosis (CF) is frequently associated with significant structural lung damage as assessed by computed tomography (CT) scanning. Using a validated CF scoring system (structural lung disease [SLD]score) we examined the degree of structural lung disease in a group of 25 children with CF who had received steroid therapy for ABPA (CF-ABPA) and compared our findings to a matched group of CF patients without ABPA (CF-CON) using both cross-section and longitudinal analysis. Further, we examined the structure-function correlation between CT findings and lung function. Mean SLD score (expressed as a percentage of maximal score) was significantly higher (worse) in the CF-ABPA group than the CF-CON group (29.3% CF-ABPA vs. 18.7% CF-CON p < .05). CF-ABPA patients showed significantly greater rate of development of structural lung disease over time than CF-CON patients (6.8% per year vs 1.4% p < .01). We found no correlation between lung function and the degree of structural lung disease. ABPA in children with CF is associated with significantly more structural lung disease than that found in children with CF without ABPA. Despite interventive steroid therapy lung disease progresses more rapidly in those patients with ABPA and CF than control patients with CF.

A COMPREHENSIVE PULMONARY REHABILITATION PROGRAM FOR THE MANAGEMENT OF POSTTUBERCULOSIS PNEUMOTHORAX: A CASE STUDY

Pulmonary tuberculosis is a contagious disease of the lung caused by mycobacterium tuberculosis. The disease is curable and preventable, but its sequelae induce structural lung damage, physiological dysfunction resulting in disability, respiratory distress, and decreased exercise capacity affecting ADLs. Pneumothorax is considered to be a major complication of TB among all the known sequelae. In the present case, the patient complained of moderate dyspnea, chest pressure, and chest pain. Based on chest radiography and a previous diagnosis of pulmonary tuberculosis, the patient was diagnosed with secondary spontaneous pneumothorax (SSP). The pneumothorax was relieved by medical intervention, i.e. by intercostal drainage, but our goal was to increase the ventilation and oxygenation of the lungs, improve airways hygiene, improve the exercise tolerance and minimize the work of breathing so that the patient can go back to his normal day-to-day activities without any trouble. A comprehensive pulmonary rehabilitation plan was structured to suit the patient's goal and was implemented and routinely followed for 1 month. It included a range of interventions like breathing exercises, airway clearance techniques, physical mobility exercises, and posture retraining. The patient demonstrated significant functional improvement in aerobic capacity, endurance, exercise tolerance capacity, and increased shoulder joint mobility. In the present case, it has also been validated that medical management anchored with Pulmonary Rehabilitation will help in gaining better outcomes.

Pathophysiology of Bronchiectasis.

Bronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome. There are multiple underlying causes including severe infections, mycobacterial disease, autoimmune conditions, hypersensitivity disorders, and genetic conditions. The pathophysiology of disease is understood in terms of interdependent concepts of chronic infection, inflammation, impaired mucociliary clearance, and structural lung damage. Neutrophilic inflammation is characteristic of the disease, with elevated levels of harmful proteases such as neutrophil elastase associated with worse outcomes. Recent data show that neutrophil extracellular trap formation may be the key mechanism leading to protease release and severe bronchiectasis. Despite the dominant of neutrophilic disease, eosinophilic subtypes are recognized and may require specific treatments. Neutrophilic inflammation is associated with elevated bacterial loads and chronic infection with organisms such as Pseudomonas aeruginosa. Loss of diversity of the normal lung microbiota and dominance of proteobacteria such as Pseudomonas and Haemophilus are features of severe bronchiectasis and link to poor outcomes. Ciliary dysfunction is also a key feature, exemplified by the rare genetic syndrome of primary ciliary dyskinesia. Mucus symptoms arise through goblet cell hyperplasia and metaplasia and reduced ciliary function through dyskinesia and loss of ciliated cells. The contribution of chronic inflammation, infection, and mucus obstruction leads to progressive structural lung damage. The heterogeneity of the disease is the most challenging aspect of management. An understanding of the pathophysiology of disease and their biomarkers can help to guide personalized medicine approaches utilizing the concept of "treatable traits."

Correlation of computed tomography findings and lung function in children and adolescents with cystic fibrosis.

The timely and appropriate monitoring of pulmonary status is of utmost importance for patients with cystic fibrosis (CF). Computed tomography (CT) has been used in clinical and research settings for tracking lung involvement in CF patients. However, as CT delivers a considerable amount of radiation, its sequential use in CF patients remains a concern. The application of CT, therefore, should take into account its potential risks. This review aims to understand whether and to what extent the CT findings correlate with the findings from other monitoring tools in CF lung disease. PubMed was searched for articles about the correlation of chest CT findings with spirometric indices and with lung clearance index in children and adolescents with CF. The most relevant articles were reviewed and are presented herein. Most studies have shown that forced expiratory volume in the first second (FEV1) and other spirometric indices correlate moderately with CT structural lung damage. However, at the individual level, there were patients with FEV1 within the normal range and abnormal CT and vice versa. Furthermore, longitudinal studies have indicated that the deterioration of structural lung damage does not occur in parallel with the progression of lung function. Lung clearance index is a better predictor of CT findings. In general, the existing studies do not support the use of lung function tests as surrogates of chest CT.

Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease.

Dysregulated protease activity has long been implicated in the pathogenesis of chronic lung diseases and especially in conditions that display mucus obstruction, such as chronic obstructive pulmonary disease, cystic fibrosis, and non-cystic fibrosis bronchiectasis. However, our appreciation of the roles of proteases in various aspects of such diseases continues to grow. Patients with muco-obstructive lung disease experience progressive spirals of inflammation, mucostasis, airway infection and lung function decline. Some therapies exist for the treatment of these symptoms, but they are unable to halt disease progression and patients may benefit from novel adjunct therapies. In this review, we highlight how proteases act as multifunctional enzymes that are vital for normal airway homeostasis but, when their activity becomes immoderate, also directly contribute to airway dysfunction, and impair the processes that could resolve disease. We focus on how proteases regulate the state of mucus at the airway surface, impair mucociliary clearance and ultimately, promote mucostasis. We discuss how, in parallel, proteases are able to promote an inflammatory environment in the airways by mediating proinflammatory signalling, compromising host defence mechanisms and perpetuating their own proteolytic activity causing structural lung damage. Finally, we discuss some possible reasons for the clinical inefficacy of protease inhibitors to date and propose that, especially in a combination therapy approach, proteases represent attractive therapeutic targets for muco-obstructive lung diseases.

P104 Multiple-breath nitrogen washout test and structural lung damage in adult patients with cystic fibrosis

P104 Multiple-breath nitrogen washout test and structural lung damage in adult patients with cystic fibrosis

IL-17A from innate and adaptive lymphocytes contributes to inflammation and damage in cystic fibrosis lung disease.

Elevated levels of interleukin (IL)-17A were detected in the airways of patients with cystic fibrosis (CF), but its cellular sources and role in the pathogenesis of CF lung disease remain poorly understood. The aim of this study was to determine the sources of IL-17A and its role in airway inflammation and lung damage in CF. We performed flow cytometry to identify IL-17A-producing cells in lungs and peripheral blood from CF patients and β-epithelial Na+ channel transgenic (Scnn1b-Tg) mice with CF-like lung disease, and determined the effects of genetic deletion of Il17a and Rag1 on the pulmonary phenotype of Scnn1b-Tg mice. T-helper 17 cells, CD3+CD8+ T-cells, γδ T-cells, invariant natural killer T-cells and innate lymphoid cells contribute to IL-17A secretion in lung tissue, lymph nodes and peripheral blood of patients with CF. Scnn1b-Tg mice displayed increased pulmonary expression of Il17a and elevated IL-17A-producing innate and adaptive lymphocytes with a major contribution by γδ T-cells. Lack of IL-17A, but not the recombination activating protein RAG1, reduced neutrophilic airway inflammation in Scnn1b-Tg mice. Genetic deletion of Il17a or Rag1 had no effect on mucus obstruction, but reduced structural lung damage and revealed an IL-17A-dependent macrophage activation in Scnn1b-Tg mice. We identify innate and adaptive sources of IL-17A in CF lung disease. Our data demonstrate that IL-17A contributes to airway neutrophilia, macrophage activation and structural lung damage in CF-like lung disease in mice. These results suggest IL-17A as a novel target for anti-inflammatory therapy of CF lung disease.

Designing Clinical Trials for Anti-Inflammatory Therapies in Cystic Fibrosis.

The inflammatory response in the CF airway begins early in the disease process and becomes persistent through life in most patients. Inflammation, which is predominantly neutrophilic, worsens airway obstruction and plays a critical role in the development of structural lung damage. While cystic fibrosis transmembrane regulator modulators will likely have a dramatic impact on the trajectory of CF lung disease over the coming years, addressing other important aspects of lung disease such as inflammation will nevertheless remain a priority. Considering the central role of neutrophils and their products in the inflammatory response, potential therapies should ultimately affect neutrophils and their products. The ideal anti-inflammatory therapy would exert a dual effect on the pro-inflammatory and pro-resolution arms of the inflammatory cascade, both of which contribute to dysregulated inflammation in CF. This review outlines the key factors to be considered in the design of clinical trials evaluating anti-inflammatory therapies in CF. Important lessons have been learned from previous clinical trials in this area and choosing the right efficacy endpoints is key to the success of any anti-inflammatory drug development program. Identifying and validating non-invasive biomarkers, novel imaging techniques and sensitive lung function tests capable of monitoring disease activity and therapeutic response are important areas of research and will be useful for the design of future anti-inflammatory drug trials.

Regarding "Serial Quantitative Chest CT Assessment of COVID-19: Deep-Learning Approach".

HomeRadiology: Cardiothoracic ImagingVol. 2, No. 3 PreviousNext Letters to the EditorFree AccessMethodologic Assessment of a Deep Learning Approach Measuring Lung Opacification in COVID-19 at Chest CTMarcelo Straus Takahashi* , Matheus Ribeiro Furtado de Mendonça†, Ian Pan§, Rogerio Zaia Pinetti‡, Felipe C. Kitamura†,ǁMarcelo Straus Takahashi* , Matheus Ribeiro Furtado de Mendonça†, Ian Pan§, Rogerio Zaia Pinetti‡, Felipe C. Kitamura†,ǁAuthor AffiliationsDepartments of Pediatric Radiology,*Artificial Intelligence,† andThoracic Radiology,‡ Diagnóstico da América SA (DASA), R. Gilberto Sabino 215, Pinheiros 05425-020 São Paulo, SP, BrazilDepartment of Radiology, Brown University Warren Alpert Medical School, Providence, RI§Department of Diagnostic Imaging, Universidade Federal de São Paulo, São Paulo, Brazilǁe-mail: [email protected]Marcelo Straus Takahashi* Matheus Ribeiro Furtado de Mendonça†Ian Pan§Rogerio Zaia Pinetti‡Felipe C. Kitamura†,ǁPublished Online:May 27 2020https://doi.org/10.1148/ryct.2020200242MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack Citations ShareShare onFacebookTwitterLinked In Editor:We read with great interest the article by Dr Huang and colleagues, published in March 2020 in Radiology: Cardiothoracic Imaging, in which they report a deep learning approach to quantify coronavirus disease 2019 (COVID-19) in chest CT (1). We are firm believers that research on artificial intelligence (AI) applied to quantitative radiology will help improve patient care in the near future. Nevertheless, we think some methodologic comments are appropriate.First, the reported model training is lacking important information essential to the reproducibility of the method; the recently published CLAIM checklist (2) addresses important points for authors presenting their research on AI applied to medical imaging. Training data annotation was done every five slices, but it is unclear whether the remaining slices were simply excluded or if some technique such as label interpolation was utilized. There was also no mention of the level at which the data were partitioned; to prevent data leakage, data should be partitioned at the patient level. The manufacturer and parameters of the scanner from which training data were obtained are also unclear. No information on the model’s loss function was reported.Second, the authors state that 8.7% of the cases were excluded due to poor segmentation, but it is unclear whether this refers only to segmentation of opacities or to the lung segmentation as well. Juxtapleural opacities are frequently reported as problematic for lung segmentation algorithms and could be a relevant issue (2). It would be interesting to know if prior structural lung damage, atelectasis, or pleural effusion affects performance (if any cases were included in the study). Also, it would be interesting to know if the model is expected to perform equally well on both lung and body kernels.Finally, there is little information on how the percentage of lung opacification (quantitative CT percentage of lung opacification [QCT-PLO] score) is measured. It is not explicit whether the algorithm is able to differentiate ground-glass opacities from consolidations or other findings, and if they all have the same weight in the final score.Despite the comments above, we believe the work done by Dr Lu Huang and colleagues is a phenomenal use case of AI to aid in prognosis and, ultimately, in patient care.Disclosures of Conflicts of Interest: M.S.T. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: employee at DASA. Other relationships: disclosed no relevant relationships. M.R.F.d.M. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: employed as a machine learning engineer at DASA. Other relationships: disclosed no relevant relationships. I.P. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: consultant at MD.ai. Other relationships: disclosed no relevant relationships. R.Z.P. disclosed no relevant relationships. F.C.K. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: consultant at MD.ai; employed at DASA. Other relationships: disclosed no relevant relationships.