Nestor L. Müller’s research while affiliated with University of British Columbia and other places

What is this page?


This page lists works of an author who doesn't have a ResearchGate profile or hasn't added the works to their profile yet. It is automatically generated from public (personal) data to further our legitimate goal of comprehensive and accurate scientific recordkeeping. If you are this author and want this page removed, please let us know.

Publications (656)


Integration and Application of Clinical Practice Guidelines for the Diagnosis of Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis
  • Literature Review

June 2022

·

213 Reads

·

36 Citations

Chest

Daniel-Costin Marinescu

·

Ganesh Raghu

·

Martine Remy-Jardin

·

[...]

·

Christopher J. Ryerson

Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were developed independently, without clear direction on how to concurrently apply their respective recommendations within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this document, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiological, and pathological features described in previous guidelines are integrated in a set of diagnostic algorithms, which are then placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. While these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases.


Diagnosis of Hypersensitivity Pneumonitis: Review and Summary of American College of Chest Physicians Statement

November 2021

·

48 Reads

·

4 Citations

The American Journal of Surgical Pathology

Assessment of lung biopsies for the diagnosis of hypersensitivity pneumonitis (HP) is one of the most difficult diagnostic problems for surgical pathologists. It is a form of interstitial lung disease resulting from an immune reaction provoked by an inhaled antigen in susceptible individuals. Although this definition sounds simple, in practice, the diagnosis of HP can be challenging. To address these issues, the American College of Chest Physicians (CHEST) has recently published a guideline for the diagnosis of HP. In this review, we will explore the multidisciplinary diagnostic evaluation of HP with a focus on the pathologic features as outlined in the CHEST guidelines. The histologic criteria are divided into 4 diagnostic categories: (1) Typical nonfibrotic HP or fibrotic HP; (2) Compatible with nonfibrotic HP or fibrotic HP; (3) Indeterminate for nonfibrotic or fibrotic HP; and (4) Alternative Diagnosis. It is important to emphasize that patterns 1 to 3 do not represent discrete histologic entities or pathologic diagnoses. Rather, these categories are meant to serve as a practical guide for organizing a complex set of overlapping histologic patterns into an integrated diagnostic framework for facilitating multidisciplinary discussion. High-resolution computed tomography features are also summarized, emphasizing how the correlation of lung biopsies with computed tomography findings can help to favor the diagnosis, particularly in cases where biopsies are not typical for HP. This review highlights details of the histologic spectrum of HP as well as the utility of different types of biopsies and bronchoalveolar lavage. We also emphasize the importance of multidisciplinary discussion and the complex differential diagnosis.


Radiological Society of North America (RSNA) Expert Consensus Statement Related to Chest CT Findings in COVID-19 Versus CO-RADS: Comparison of Reporting System Performance Among Chest Radiologists and End-User Preference

November 2020

·

43 Reads

·

19 Citations

Canadian Association of Radiologists Journal

Purpose: The RSNA expert consensus statement and CO-RADS reporting system assist radiologists in describing lung imaging findings in a standardized manner in patients under investigation for COVID-19 pneumonia and provide clarity in communication with other healthcare providers. We aim to compare diagnostic performance and inter-/intra-observer among chest radiologists in the interpretation of RSNA and CO-RADS reporting systems and assess clinician preference. Methods: Chest CT scans of 279 patients with suspected COVID-19 who underwent RT-PCR testing were retrospectively and independently examined by 3 chest radiologists who assigned interpretation according to the RSNA and CO-RADS reporting systems. Inter-/intra-observer analysis was performed. Diagnostic accuracy of both reporting systems was calculated. 60 clinicians participated in a survey to assess end-user preference of the reporting systems. Results: Both systems demonstrated almost perfect inter-observer agreement (Fleiss kappa 0.871, P < 0.0001 for RSNA; 0.876, P < 0.0001 for CO-RADS impressions). Intra-observer agreement between the 2 scoring systems using the equivalent categories was almost perfect (Fleiss kappa 0.90-0.92, P < 0.001). Positive predictive values were high, 0.798-0.818 for RSNA and 0.891-0.903 CO-RADS. Negative predictive value were similar, 0.573-0.585 for RSNA and 0.573-0.58 for CO-RADS. Specificity differed between the 2 systems, 68-73% for CO-RADS and 52-58% for RSNA with superior specificity of CO-RADS. Of 60 survey participants, the majority preferred the RSNA reporting system rather than CO-RADS for all options provided (66.7-76.7%; P < 0.05). Conclusions: RSNA and CO-RADS reporting systems are consistent and reproducible with near perfect inter-/intra-observer agreement and excellent positive predictive value. End-users preferred the reporting language in the RSNA system.


Chest CT target sign in a couple with COVID-19 pneumonia
  • Article
  • Full-text available

August 2020

·

76 Reads

·

37 Citations

Radiologia Brasileira

We describe a target sign on chest CT characterized by a combination of peripheral ring-like opacity and a central nodular ground-glass opacity surrounding a vessel in a couple with COVID-19 pneumonia confirmed by real-time reverse transcriptase fluorescence polymerase chain reaction sputum analysis.

Download

Figure 1. Bilateral posterior and peripheral predominant ground-glass opacities in (A) (short arrows), with a slightly more rounded appearance in (B) (short arrows).
Figure 2. Examples of bilateral peripheral posterior predominant consolidation with perilobular morphology consistent with organizing pneumonia reaction pattern. Examples of perilobular arcades are demonstrated in (A) (short arrows) and areas of subpleural sparing in (B) (arrowheads). Magnified image of perilobular arcades demonstrated in (C).
Figure 3. Examples of rounded peribronchovascular ground-glass opacities, slightly ill-defined in (A) and (B) (short arrows) and more confluent and well demarcated in (C) (long arrows).
Figure 4. Spectrum of ground-glass opacities with peripheral predominance in (A) and (B) (short arrows).
Figure 5. Spectrum of organizing pneumonia reaction pattern (short arrows) ranging from mild in (A), with peripheral crescentic, perilobular consolidation and central ground glass consistent with the ''reverse halo'' sign (long arrow) demonstrated in the left lower lobe in (B) and parenchymal distortion demonstrated in (C) and (D).

+3

RSNA Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19: Interobserver Agreement Between Chest Radiologists

July 2020

·

941 Reads

·

38 Citations

Canadian Association of Radiologists Journal

Purpose To assess the interobserver variability between chest radiologists in the interpretation of the Radiological Society of North America (RSNA) expert consensus statement reporting guidelines in patients with suspected coronavirus disease 2019 (COVID-19) pneumonia in a setting with limited reverse transcription polymerase chain reaction testing availability. Methods Chest computed tomography (CT) studies in 303 consecutive patients with suspected COVID-19 were reviewed by 3 fellowship-trained chest radiologists. Cases were assigned an impression of typical, indeterminate, atypical, or negative for COVID-19 pneumonia according to the RSNA expert consensus statement reporting guidelines, and interobserver analysis was performed. Objective CT features associated with COVID-19 pneumonia and distribution of findings were recorded. Results The Fleiss kappa for all observers was almost perfect for typical (0.815), atypical (0.806), and negative (0.962) COVID-19 appearances ( P < .0001) and substantial (0.636) for indeterminate COVID-19 appearance ( P < .0001). Using Cramer V analysis, there were very strong correlations between all radiologists’ interpretations, statistically significant for all (typical, indeterminate, atypical, and negative) COVID-19 appearances ( P < .001). Objective CT imaging findings were recorded in similar percentages of typical cases by all observers. Conclusion The RSNA expert consensus statement on reporting chest CT findings related to COVID-19 demonstrates substantial to almost perfect interobserver agreement among chest radiologists in a relatively large cohort of patients with clinically suspected COVID-19. It therefore serves as a reliable reference framework for radiologists to accurately communicate their level of suspicion based on the presence of evidence-based objective findings.



Chronic Pulmonary Microaspiration High-resolution Computed Tomographic Findings in 13 Patients

May 2014

·

93 Reads

·

14 Citations

Journal of Thoracic Imaging

Purpose: The aim of the study was to describe the high-resolution computed tomography (CT) manifestations of chronic pulmonary microaspiration, a condition characterized by recurrent subclinical aspiration of small droplets of gastric contents or foreign particles into the lungs. Materials and methods: We reviewed the CT findings in 13 consecutive patients with clinical (n=13) and histologic (n=1) diagnosis of chronic pulmonary microaspiration. Twelve patients presented with persistent cough, but none had a clinical history of acute aspiration. One patient was asymptomatic. All patients had volumetric CT of the chest reconstructed using thin sections (1 to 1.3 mm) at the time of diagnosis. The CT scans were interpreted by 3 chest radiologists who reached a final decision by consensus. Results: All 13 patients had centrilobular nodules and ground-glass opacities that involved mainly the dependent lung regions in 11 patients and had a random distribution in 2. Other common findings included branching opacities (n=10), small foci of consolidation (n=7), septal lines (n=5), and bronchiectasis (n=7). The 13 patients had at least 1 risk factor for aspiration including gastroesophageal reflux (n=9), hiatus hernia (n=6), esophageal dysfunction (n=3), oropharyngeal dysphagia (n=1), esophageal carcinoma (n=1), and use of sedatives (n=2). Conclusions: The high-resolution CT manifestations of chronic pulmonary microaspiration consist mainly of centrilobular nodules and ground-glass opacities that tend to involve predominately the dependent regions. Branching opacities and small foci of consolidation are seen in the majority of cases.


COPD phenotypes in biomass smoke-versus tobacco smoke-exposed Mexican women

October 2013

·

85 Reads

·

182 Citations

European Respiratory Journal

We hypothesised that biomass smoke exposure is associated with an airway-predominant chronic obstructive pulmonary disease (COPD) phenotype, while tobacco-related COPD is associated with an emphysema-predominant phenotype. In this cross-sectional study, female never-smokers with COPD and biomass exposure (n=21) and female ex-cigarette smokers with COPD without biomass exposure (n=22) completed computed tomography (CT) at inspiration and expiration, pulmonary function, blood gas, exercise tolerance, and quality of life measures. Two radiologists scored the extent of emphysema and air trapping on CT. Quantitative emphysema severity and distribution and airway wall thickness were calculated using specialised software. Women in the tobacco group had significantly more emphysema than the biomass group (radiologist score 2.3 versus 0.7, p=0.001; emphysema on CT 27% versus 19%, p=0.046; and a larger size of emphysematous spaces, p=0.006). Women in the biomass group had significantly more air trapping than the tobacco group (radiologist score 2.6 and 1.5, respectively; p=0.02) and also scored lower on the symptom, activities and confidence domains of the quality of life assessment and had lower oxygen saturation at rest and during exercise (p<0.05). Biomass smoke exposure is associated with less emphysema but more air trapping than tobacco smoke exposure, suggesting an airway-predominant phenotype.


The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: A prospective analysis from the ECLIPSE study

April 2013

·

125 Reads

·

259 Citations

The Lancet Respiratory Medicine

Emphysema is a key contributor to airflow limitation in chronic obstructive pulmonary disease (COPD) and can be quantified using CT scanning. We investigated the change in CT lung density in a longitudinal, international cohort of patients with COPD. We also explored the potential relation between emphysema and patient characteristics, and investigated if certain circulating biomarkers were associated with decline in CT lung density. We used a random coefficient model to assess predictors of both CT lung density and its longitudinal change over 3 years in 1928 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Lung density was measured for every voxel in the CT scan and after correcting for lung volume was expressed as the density at lowest 15th percentile point of the distribution. This study is registered with ClinicalTrials.gov, number NCT00292552. Lung density at baseline was influenced by age, sex, body-mass index, current smoking status and smoking history, and severity of airflow limitation. The observed decline in lung density was variable (mean decline -1·13 g/L [SE 0·06] per year). The annual decline in lung density was more rapid in women (additional -0·41 [SE 0·14] g/L per year, p=0·003) than men and in current smokers (additional -0·29 [SE 0·14] g/L per year, p=0·047) than in former smokers. Circulating levels of the biomarkers surfactant protein D (SP-D) and soluble receptor for advanced glycation endproduct (sRAGE) were significantly associated with both baseline lung density and its decline over time. This study shows that decline in lung density in COPD can be measured, that it is variable, and related to smoking and gender. We identified potential biochemical predictors of the presence and progression of emphysema. GlaxoSmithKline.


Interobserver Variability in the CT Assessment of Honeycombing in the Lungs

December 2012

·

153 Reads

·

357 Citations

Radiology

Purpose: To quantify observer agreement and analyze causes of disagreement in identifying honeycombing at chest computed tomography (CT). Materials and methods: The institutional review board approved this multiinstitutional HIPAA-compliant retrospective study, and informed patient consent was not required. Five core study members scored 80 CT images with a five-point scale (5 = definitely yes to 1 = definitely no) to establish a reference standard for the identification of honeycombing. Forty-three observers from various subspecialties and geographic regions scored the CT images by using the same scoring system. Weighted κ values of honeycombing scores compared with the reference standard were analyzed to investigate intergroup differences. Images were divided into four groups to allow analysis of imaging features of cases in which there was disagreement: agreement on the presence of honeycombing, agreement on the absence of honeycombing, disagreement on the presence of honeycombing, and other (none of the preceding three groups applied). Results: Agreement of scores of honeycombing presence by 43 observers with the reference standard was moderate (Cohen weighted κ values: 0.40-0.58). There were no significant differences in κ values among groups defined by either subspecialty or geographic region (Tukey-Kramer test, P = .38 to >.99). In 29% of cases, there was disagreement on identification of honeycombing. These cases included honeycombing mixed with traction bronchiectasis, large cysts, and superimposed pulmonary emphysema. Conclusion: Identification of honeycombing at CT is subjective, and disagreement is largely caused by conditions that mimic honeycombing.


Citations (21)


... Установление диагноза имеет решающее значение для выбора тактики лечения и определения прогноза. Исключение дальнейшего контакта с выявленным антигеном и рассмотрение вопроса о проведении иммуносупрессивной терапии играют значимую роль при ведении пациентов с фГП, в то время как при ИЛФ необходимо раннее назначение антифибротической терапии [4,[8][9][10]. ...

Reference:

Biomarkers and genetic predictors of hypersensitivity pneumonitis
Integration and Application of Clinical Practice Guidelines for the Diagnosis of Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis
  • Citing Article
  • June 2022

Chest

... In the majority of these studies, the history of exposure was questioned by pulmonologists. Moreover, the decision was not taken from the diagnosis of the patients together with histopathological findings [25,37]. Our research benefits from the comprehensive investigation with the addition of an occupational medicine physician to the MDD team [38]. ...

Diagnosis of Hypersensitivity Pneumonitis: Review and Summary of American College of Chest Physicians Statement
  • Citing Article
  • November 2021

The American Journal of Surgical Pathology

... In view of these various findings and suggestions, several reporting systems have been recommended for reporting the chest radiographic and CT results of patients who are suspected of having COVID-19 in a high-disease-prevalence setting [7][8][9][10][11][12]. These systems provide standardized language and diagnostic categories to establish the likelihood that certain lung abnormalities on CT images represent COVID-19, although inter-observer agreements for establishing each category in these reporting systems vary [7][8][9][10][11][12][13][14][15][16][17]. Several studies have therefore used artificial intelligences (AIs) with various approaches for diagnosis of COVID-19 [18][19][20]. ...

Radiological Society of North America (RSNA) Expert Consensus Statement Related to Chest CT Findings in COVID-19 Versus CO-RADS: Comparison of Reporting System Performance Among Chest Radiologists and End-User Preference
  • Citing Article
  • November 2020

Canadian Association of Radiologists Journal

... A aplicação da inteligência artificial na descoberta da vacina para o Covid-19 foi uma ferramenta crucial para acelerar o processo de desenvolvimento e garantir a eficácia e segurança da vacina. Os métodos utilizados para coletar, analisar e sintetizar grandes quantidades de dados permitiram aos pesquisadores identificar as melhores estratégias para combater a doença em um curto período (Müller, 2020). ...

Chest CT target sign in a couple with COVID-19 pneumonia

Radiologia Brasileira

... The accuracy of readers' interpretations of COVID-19 diagnostic CT chest images has previously been researched, but those studies were limited by small sample sizes, diverse levels of case difficulty, and the involvement of readers with varying degrees of expertise (Bai et al., 2020;Bellini et al., 2021;Brun et al., 2021;Byrne et al., 2021;de Jaegere et al., 2020;Dilek et al., 2021;Hadied et al., 2020;Koşar et al., 2021;Nivet et al., 2021;Revel et al., 2021). These limitations can be primarily attributed to the fact that most such studies were conducted in clinical settings, where it is impossible to control for case difficulty or reader experience and where participant numbers are limited. ...

RSNA Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19: Interobserver Agreement Between Chest Radiologists

Canadian Association of Radiologists Journal

... Chronic pulmonary microaspiration (CPM) is one of the complications which have received much attention despite its low incidence (1.4 to 6 per 10,000). Aspiration pneumonia has been accounted for 5-15% of community-acquired pneumonia cases 1,[5][6][7][8] . Aspiration pneumonia is one of the most leading causes of death in subjects with dysphagia, with an estimated case between 300,000 and 6,000,000 annually in the United States 3 Clinical outcomes of CPM are a range of uncomplicated changes to severe respiratory problems and even death. ...

Chronic Pulmonary Microaspiration High-resolution Computed Tomographic Findings in 13 Patients
  • Citing Article
  • May 2014

Journal of Thoracic Imaging

... Consistent with established practice, emphysema was defined as lung parenchyma with attenuation values of less than −950 hounsfield units at inspiration. [18][19][20] For each CT dataset, an emphysema ratio was generated, which is defined as the percentage of lung volume with emphysema divided by total lung volume. ...

The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: A prospective analysis from the ECLIPSE study
  • Citing Article
  • April 2013

The Lancet Respiratory Medicine

... It has been reported that smokers are more likely to develop emphysema than those exposed to biomass fuel. Camp et al. found that female COPD patients exposed to biomass smoke had less emphysema but more air retention than those exposed to e-tobacco smoke, suggesting that biofuel-induced COPD may be a respiratory tract-dominated phenotype 11 . In this study, we found that men had more emphysema, bullae, and interstitial lung abnormalities, but lower FEV 1 /FVC ratios than women, demonstrating these same findings in our study. ...

COPD phenotypes in biomass smoke-versus tobacco smoke-exposed Mexican women
  • Citing Article
  • October 2013

European Respiratory Journal

... The chest CT findings were classified as follows: (a) ground-glass opacity, defined as increased density of the lung parenchyma that retains the visible contours of the vessels and bronchi inside the affected area; (b) vascular enhancement sign (VES), vascular enlargement inside the lesion resulting from congestion and dilation of small vessels; (c) septal thickening; (d) crazy-paving pattern appearing as thickened interlobular septa and intralobular lines superimposed on a background of groundglass opacity; (e) consolidation, when the air in the alveolar space is supplanted by a pathological product; and (f) parenchymal band, appearing as a linear opacity, usually 1-3 mm thick and up to 5 cm long that usually extends to the visceral pleura (16)(17)(18). ...

Consenso brasileiro ilustrado sobre a terminologia dos descritores e padrões fundamentais da TC de tórax

Jornal Brasileiro de Pneumologia

... Qualitative and semiquantitative visual assessments of disease extent in ILDs have been adopted, the latter striving for quantification and standardization of the evaluation of disease extent in comparison to the former. However, both approaches suffer from moderate to high inter-reader variability (kappa value ranging from 0.28 to 0.85) [28], necessitate description of the location of the abnormalities allowing a basic quantification of ILD severity [29][30][31]. ...

Interobserver Variability in the CT Assessment of Honeycombing in the Lungs
  • Citing Article
  • December 2012

Radiology