Effects of ageing and smoking on pulmonary computed tomography scans using parametric response mapping

Boudewijn, Ilse M.; Postma, Dirkje S.; Telenga, Eef D.; Hacken, Nick H. T. ten; Timens, Wim; Oudkerk, Matthijs; Ross, Brian D.; Galbán, Craig J.; Berge, Maarten van den

doi:10.1183/09031936.00009415

Cited by 32 publications

(25 citation statements)

References 15 publications

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“…There were no significant differences in values of the VH markers R5-R20 and S acin across GINA treatment intensity groups. Of the 3 of 41 asthmatic patients with a smoking history of more than 15 pack years, all had a PRM emphysema (PRM Emph ) score that was less than the mean 1 1.96 SD (5% PRM Emph ) in a healthy agematched population of 98 subjects 38 and preserved carbon monoxide transfer coefficient percent predicted values (Table I). The 3 patients all had evidence of asthma objectively (1 had 78% FEV 1 reversibility, 1 had a PC 20 methacholine value of 2 mg/ mL, and 1 had 49% FEV 1 reversibility).…”

Section: Resultsmentioning

confidence: 99%

Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

Bell

Foy

Richardson

et al. 2019

Journal of Allergy and Clinical Immunology

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Background: Asthma is a disease characterized by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived by using impulse oscillometry (IOS) or multiple-breath washout (MBW) are associated with key asthmatic patient-related outcome measures and airways hyperresponsiveness. However, the topographical mechanisms of VH in the lung remain poorly understood. Objectives: We hypothesized that specific regionalization of topographical small-airway disease would best account for IOSand MBW-measured indices in patients. Methods: We evaluated the results of paired expiratory/ inspiratory computed tomography in a cohort of asthmatic (n 5 41) and healthy (n 5 11) volunteers to understand the determinants of clinical VH indices commonly reported by

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Section: Resultsmentioning

confidence: 99%

Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

Bell

Foy

Richardson

et al. 2019

Journal of Allergy and Clinical Immunology

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“…For this study, patients with persistent asthma were included, based on the presence of bronchial hyper-responsiveness after methacholine challenges, characteristic asthma symptoms and a doctor's diagnosis of asthma 26 . In parallel, sixteen healthy controls were included with no history of respiratory disease, normal spirometry and absence of bronchial hyperresponsiveness (NORM study 27,28 ). The NORM study was also approved by the Medical Ethical Committee of the University Medical Center Groningen and participants gave their informed consent.…”

Section: Patient Selection and Cd4 + T Cell Isolation From Pbmcs Thementioning

confidence: 99%

Smooth-muscle-derived WNT5A augments allergen-induced airway remodelling and Th2 type inflammation

Koopmans

Hesse

Nawijn

et al. 2020

Sci Rep

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Asthma is a heterogeneous disease characterized by chronic inflammation and structural changes in the airways. The airway smooth muscle (ASM) is responsible for airway narrowing and an important source of inflammatory mediators. We and others have previously shown that WNT5A mRNA and protein expression is higher in the ASM of asthmatics compared to healthy controls. Here, we aimed to characterize the functional role of (smooth muscle-derived) WNT5A in asthma. We generated a tet-ON smooth-muscle-specific WNT5A transgenic mouse model, enabling in vivo characterization of smoothmuscle-derived WNT5A in response to ovalbumin. Smooth muscle specific WNT5A overexpression showed a clear trend towards enhanced actin (α-SMA) expression in the ASM in ovalbumin challenged animals, but had no effect on collagen content. WNT5A overexpression in ASM also significantly enhanced the production of the Th2-cytokines IL4 and IL5 in lung tissue after ovalbumin exposure. In line with this, WNT5A increased mucus production, and enhanced eosinophilic infiltration and serum IgE production in ovalbumin-treated animals. In addition, CD4 + T cells of asthma patients and healthy controls were stimulated with WNT5A and changes in gene transcription assessed by RNA-seq. WNT5A promoted expression of 234 genes in human CD4 + T cells, among which the Th2 cytokine IL31 was among the top 5 upregulated genes. IL31 was also upregulated in response to smooth muscle-specific WNT5A overexpression in the mouse. In conclusion, smooth-muscle derived WNT5A augments Th2 type inflammation and remodelling. Our findings imply a pro-inflammatory role for smooth musclederived WNT5A in asthma, resulting in increased airway wall inflammation and remodelling. Asthma is a heterogeneous disease characterized by chronic inflammation of the large and small airways. More than 200 million people worldwide are estimated to be affected by asthma 1. Asthma is characterized by episodic changes in respiratory symptoms such as breathlessness, wheezing, chest tightness and coughing, reflecting airway hyper-responsiveness (AHR). Apart from this variable component of AHR, asthma is characterized by the development of structural changes in the airways, termed airway remodelling, which contribute to airflow obstruction 2. Airway smooth muscle (ASM) is a central player in the pathology of asthma. Airway smooth muscle thickness correlates with asthma severity and lung function 3. In line with this, bronchial thermoplasty (BT) results in diminished ASM mass in severe asthmatics for up to at least two years 4 , which is associated with improvement in quality of life, and a reduction in symptoms and number of exacerbations 5. ASM cells are major

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“…The emphysema and AT thresholds (À950 HU and À856 HU, respectively) have been previously defined and are used for CT analysis in the COPDGene clinical trial (9)(10)(11)(12). The upper limit on the inspiratory CT (À810 HU) was determined using healthy smokers accrued as part of the NORM trial (5,13). Global PRM measures were presented as relative lung volumes.…”

Section: Parametric Response Mapmentioning

confidence: 99%

Parametric Response Mapping of Bronchiolitis Obliterans Syndrome Progression After Lung Transplantation

Verleden

Vos

Vandermeulen

et al. 2016

American Journal of Transplantation

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Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation. Air trapping and mosaic attenuation are typical radiological features of BOS, however quantitative evaluation remains troublesome. We evaluated parametric response mapping (PRM, voxel-to-voxel comparison of inspiratory and expiratory CT scans) in lung transplant recipients diagnosed with BOS (n=20) and time-matched stable lung transplant recipients (n=20). Serial PRM measurements were performed pre-diagnosis, at time of BOS diagnosis and post-diagnosis (Tpre, T0 and Tpost respectively); or at a post-operatively matched time in stable patients. PRM results were correlated with pulmonary function and confirmed by microCT analysis of end-stage explanted lung tissue. We observed by PRM an increase in functional small airway disease (fSAD), from Tpre to T0 (p=0.006) and a concurrent decrease in healthy parenchyma (p=0.02) in the BOS group. This change in PRM continued to Tpost, which was significantly different compared to the stable patients (p=0.0002). At BOS diagnosis, the increase in fSAD was strongly associated with a decrease in FEV1 (p=0.011). MicroCT confirmed the presence of airway obliteration in a sample of a BOS patient identified with 67% fSAD by PRM. We demonstrated the use of PRM as an adequate readout to monitor BOS progression in lung transplant recipients.

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Effects of ageing and smoking on pulmonary computed tomography scans using parametric response mapping

Cited by 32 publications

References 15 publications

Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

Smooth-muscle-derived WNT5A augments allergen-induced airway remodelling and Th2 type inflammation

Parametric Response Mapping of Bronchiolitis Obliterans Syndrome Progression After Lung Transplantation

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