Pulmonary Dysfunction after Treatment for Childhood Cancer. Comparing Multiple-Breath Washout with Spirometry

Schindera, Christina; Usemann, Jakob; Zuercher, Simeon; Jung, Ruedi; Kasteler, Rahel; Frauchiger, Bettina Sarah; Naumann, Geraldine; Rueegg, Corina S.; Latzin, Philipp; Kuehni, Claudia E.; Weid, Nicolas X. von der

doi:10.1513/annalsats.202003-211oc

Cited by 7 publications

(13 citation statements)

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“…In this cohort, 49% of included survivors had one or more pulmonary function parameter below the LLN. In an independent Swiss study including 17 survivors exposed to lung toxic treatment, proportions with FEV1 and FVC below LLN were similar 34 . The proportion of survivors with obstruction, restriction or diffusion capacity impairment (31%) was slightly lower than in a longitudinal study from the US by Armenian et al with similar, but slightly more conservative, cut‐off values for obstructive disease, restrictive disease and DLCO impairment (46%),9 a single center US study by Green et al 30 with an older patient population (65%, median ages: 34 and 17 years, respectively) and a Dutch study by Mulder et al 29 (44%).…”

Section: Discussionmentioning

confidence: 85%

Longitudinal assessment of lung function in Swiss childhood cancer survivors—A multicenter cohort study

Kasteler,

Otth,

Halbeisen

et al. 2023

Pediatric Pulmonology

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ObjectiveChildhood cancer survivors are at risk for pulmonary morbidity due to exposure to lung‐toxic treatments, including specific chemotherapeutics, radiotherapy, and surgery. Longitudinal data on lung function and its change over time are scarce. We investigated lung function trajectories in survivors over time and the association with lung‐toxic treatments.MethodsThis retrospective, multicenter cohort study included Swiss survivors diagnosed between 1990 and 2013 and exposed to lung‐toxic chemotherapeutics or thoracic radiotherapy. Pulmonary function tests (PFTs), including forced expiration volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, total lung capacity, and diffusion capacity of the lung for carbon monoxide, were obtained from hospital charts. We calculated z‐scores and percentage predicted, described lung function over time, and determined risk factors for change in FEV1 and FVC using multivariable linear regression.ResultsWe included 790 PFTs from 183 survivors, with a median age of 12 years at diagnosis and 5.5 years of follow‐up. Most common diagnosis was lymphoma (55%). Half (49%) of survivors had at least one abnormal pulmonary function parameter, mainly restrictive (22%). Trajectories of FEV1 and FVC started at z‐scores of −1.5 at diagnosis and remained low throughout follow‐up. Survivors treated with thoracic surgery started particularly low, with an FEV1 of −1.08 z‐scores (−2.02 to −0.15) and an FVC of −1.42 z‐scores (−2.27 to −0.57) compared to those without surgery.ConclusionReduced pulmonary function was frequent but mainly of mild to moderate severity. Nevertheless, more research and long‐term surveillance of this vulnerable population is needed.

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Section: Discussionmentioning

confidence: 85%

Longitudinal assessment of lung function in Swiss childhood cancer survivors—A multicenter cohort study

Kasteler,

Otth,

Halbeisen

et al. 2023

Pediatric Pulmonology

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“…In this cohort, 49% of included survivors had one or more pulmonary function outcomes below the LLN. In an independent Swiss study including 17 survivors exposed to lung toxic treatment, proportions with FEV1 and FVC below LLN were similar (43). The proportion of survivors with at least one condition (31%) was slightly lower than in a longitudinal study from the US by Armenian et al with similar, but slightly more conservative, cut-off values for obstructive disease, restrictive disease and DLCO impairment (46%), a single center US study by Green et al with an older patient population (65%) and a Dutch study by Mulder et al (44%) (11, 39, 44).…”

Section: Discussionmentioning

confidence: 99%

“…Spirometry and body plethysmography are most commonly used to follow up survivors but may not be sensitive enough to detect subtle changes occurring in the lung periphery. Therefore, two recent studies used inert gas washout techniques in survivors (43, 50). Both studies could show that the test is feasible in survivors, even in younger children.…”

Section: Discussionmentioning

confidence: 99%

“…In this cohort, 49% of included survivors had one or more pulmonary function outcomes below the LLN. In an independent Swiss study including 17 survivors exposed to lung toxic treatment, proportions with FEV1 and FVC below LLN were similar (43) (45). In Switzerland the screening mostly consists of spirometry and bodyplethysmography, survivors are less often referred for DLCO testing (46).…”

Section: Prevalence Of Abnormal Pft Measurementsmentioning

confidence: 99%

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Longitudinal assessment of lung function in Swiss childhood cancer survivors

Kasteler

Otth

Halbeisen

et al. 2022

Preprint

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Rationale Childhood cancer survivors (CCSs) are at increased risk for pulmonary morbidity due to exposure to lung-toxic treatments, including specific chemotherapies, radiotherapy, and surgery. Longitudinal data on lung function, with information on how outcomes change over time, in CCSs are scarce. Objectives To investigate lung function trajectories in childhood cancer survivors over time and investigate the association with lung-toxic treatment. Methods This retrospective, multi-center cohort study included CCSs, who were diagnosed between 1990 and 2013 in Switzerland and had been exposed to lung-toxic chemotherapeutics or thoracic radiotherapy. Pulmonary function tests (PFTs) were obtained from hospital charts. We assessed quality of PFTs systematically and calculated z-scores and percentage predicted of forced expiratory volume in first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC) and diffusion capacity for carbon-monoxide (DLCO) based on recommended reference equations. We described lung function over time and determined risk factors for change in FEV1 and FVC using multivariable linear regression. Results We included 790 PFTs from 183 CCSs, with a median age of 12 years (IQR 7 to 14) at diagnosis. Common diagnoses were lymphoma (55%), leukemia (11%) and CNS tumors (12%). Median follow-up time was 5.5 years. Half (49%) of CCSs had at least one abnormal pulmonary function parameter, with restrictive impairment being common (22%). Trajectories of FEV1 and FVC started at z-scores of -1.5 at diagnosis and remained low throughout follow-up. CCSs treated with thoracic surgery started particularly low, with an FEV1 of -1.08 z-scores (-2.02 to -0.15) and an FVC of -1.42 z-scores (-2.27 to -0.57) compared to those without surgery. In CCS exposed to lung-toxic chemotherapeutics FEV1 z-scores increased slightly over time (0.12 per year; 95%CI 0.02 to 0.21). Conclusion The large proportion of CCSs with reduced lung function identified in this study underlines the need for more research and long-term surveillance of this vulnerable population.

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“…Studies on CF ( 33 ), primary ciliary dyskinesia ( 34 ), and non-CF bronchiectasis ( 35 ) demonstrated a correlation between abnormal LCI and structural lung disease. A recent study has demonstrated the superiority of MBW compared with spirometry in detecting pulmonary dysfunction in long-term survivors of childhood cancer ( 36 ). MBW is a promising method for the assessment of the lungs in PADs ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Multiple Breath Washout for Early Assessment of Pulmonary Complications in Patients With Primary Antibody Deficiencies: An Observational Study in Pediatric Age

et al. 2022

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BackgroundIn primary antibody deficiencies (PADs), pulmonary complications are the main cause of morbidity, despite immunoglobulin substitutive therapy, antibiotic treatment of exacerbations, and respiratory physiotherapy. Current Italian recommendations for surveillance of PADs respiratory complications include an annual assessment of spirometry and execution of chest high-resolution computed tomography (HRCT) every 4 years.ObjectiveThis study aimed to evaluate the effectiveness of the lung clearance index (LCI) as an early marker of lung damage in patients with PADs. LCI is measured by multiple breath washout (MBW), a non-invasive and highly specific test widely used in patients with cystic fibrosis (CF).MethodsPediatric patients with PADs (n = 17, 10 male, 7 female, and age range 5–15 years) underwent baseline assessment of lung involvement with chest HRCT, spirometry, and multiple breath nitrogen washout. Among them, 13 patients were followed up to repeat HRCT after 4 years, while performing pulmonary function tests annually. Their baseline and follow-up LCI and forced expiratory volume at 1 s (FEV1) values were compared, taking HRCT as the gold standard, using logistic regression analysis.ResultsLung clearance index [odds ratio (OR) 2.3 (confidence interval (CI) 0.1–52) at baseline, OR 3.9 (CI 0.2–191) at follow-up] has a stronger discriminating power between altered and normal HRCT rather than FEV1 [OR 0.6 (CI 0.2–2) at baseline, OR 1.6 (CI 0.1–13.6) at follow-up].ConclusionWithin the context of a limited sample size, LCI seems to be more predictive of HRCT alterations than FEV1 and more sensitive than HRCT in detecting non-uniform ventilation in the absence of bronchiectasis. A study of a larger cohort of pediatric patients followed longitudinally in adulthood is needed to challenge these findings.

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Pulmonary Dysfunction after Treatment for Childhood Cancer. Comparing Multiple-Breath Washout with Spirometry

Abstract: All authors edited, reviewed, and approved the final version of the manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are investigated and resolved.

Cited by 7 publications

References 29 publications

Longitudinal assessment of lung function in Swiss childhood cancer survivors—A multicenter cohort study

Longitudinal assessment of lung function in Swiss childhood cancer survivors—A multicenter cohort study

Longitudinal assessment of lung function in Swiss childhood cancer survivors

Multiple Breath Washout for Early Assessment of Pulmonary Complications in Patients With Primary Antibody Deficiencies: An Observational Study in Pediatric Age

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