Feasibility of dynamic chest radiography to calculate lung volumes in adult people with cystic fibrosis: a pilot study.

INTRODUCTION: Dynamic chest radiography (DCR) is a novel, low-dose, real-time digital imaging system where software identifies moving thoracic structures and can automatically calculate lung areas. In an observational, prospective, non-controlled, single-centre pilot study, we compared it with whole-body plethysmography (WBP) in the measurement of lung volume subdivisions in people with cystic fibrosis (pwCF). METHODS: Lung volume subdivisions were estimated by DCR using projected lung area (PLA) during deep inspiration, tidal breathing and full expiration, and compared with same-day WBP in 20 adult pwCF attending routine review. Linear regression models to predict lung volumes from PLA were developed. RESULTS: Total lung area (PLA at maximum inspiration) correlated with total lung capacity (TLC) (r=0.78, p<0.001), functional residual lung area with functional residual capacity (FRC) (r=0.91, p<0.001), residual lung area with residual volume (RV) (r=0.82, p=0.001) and inspiratory lung area with inspiratory capacity (r=0.72, p=0.001). Despite the small sample size, accurate models were developed for predicting TLC, RV and FRC. CONCLUSION: DCR is a promising new technology that can be used to estimate lung volume subdivisions. Plausible correlations between plethysmographic lung volumes and DCR lung areas were identified. Further studies are needed to build on this exploratory work in both pwCF and individuals without CF. TRIAL REGISTRATION NUMBER: ISRCTN64994816.

Eruptive melanocytic naevi following initiation of elexacaftor/ivacaftor/tezacaftor for cystic fibrosis.

A 29 year old woman with cystic fibrosis (CF) presented to CF clinic following the sudden development of over 200 pigmented naevi located predominately on the trunk and limbs 3 months after commencing elexacaftor/tezacaftor/ivacaftor, a novel triple-therapy CFTR modulator therapy for CF. Skin biopsy confirmed benign naevi and the clinical presentation was consistent with eruptive melanocytic naevi. Elexacaftor/tezacaftor/ivacaftor received marketing authorisation in August 2020 and this is the first report of associated naevi. The individual described here remains clinically well, and continues on elexacaftor/tezacaftor/ivacaftor with dermatology follow-up.

Cardiac sarcoidosis in an adult person with cystic fibrosis: a case report.

Cardiac sarcoidosis and cystic fibrosis (CF) are both rare conditions and their co-existence has not previously been noted in adults. For the first time we report a case of isolated cardiac sarcoidosis in a woman with CF, and discuss the possible combined aetiological factors. As the life expectancy of people with CF continues to increase, clinicians should be aware of the emergence of concomitant inflammatory conditions typically diagnosed in adulthood, and the diagnostic challenges this may present.

Use of Dynamic Chest Radiography to Assess Treatment of Pulmonary Exacerbations in Cystic Fibrosis.

Background Although spirometry is an important marker in the management of pulmonary exacerbations in cystic fibrosis (CF), it is a forced maneuver and can generate aerosol. Therefore, it may be difficult to perform in some individuals. Dynamic chest radiography (DCR) provides real-time information regarding pulmonary dynamics alongside fluoroscopic-style thoracic imaging. Purpose To assess the effect of pulmonary exacerbation treatment by using both spirometry and DCR and assess the clinical utility of DCR in participants with CF experiencing pulmonary exacerbations. Materials and Methods In this prospective, observational, single-center pilot study, spirometry and DCR were performed before and after treatment of pulmonary exacerbations in participants with CF between December 2019 and August 2020. Spirometry measured forced expiratory volume in 1 second (FEV1) and forced vital capacity. DCR helped to measure projected lung area (PLA), hemidiaphragm midpoint position, and speed during tidal and deep breathing. Data were analyzed by using the paired t test or Wilcoxon signed-rank test. Correlation was assessed by using the Spearman rank correlation coefficient. Results Twenty participants with CF (mean age, 25 years ± 7 [standard deviation]; 14 women) were evaluated. Spirometry showed that percentage predicted FEV1 improved from a median of 44% (interquartile range [IQR], 17%) before treatment to 55% (IQR, 16%) after treatment (P = .004). DCR showed improvement in median deep breathing excursion for left and right hemidiaphragms (from 18 [IQR, 11] to 25 [IQR, 16] mm [P = .03] and from 13 [IQR, 6] to 19 [IQR, 14] mm [P = .03], respectively) and in median expiratory speed following deep breathing for left and right hemidiaphragms (from 7 [IQR, 2] to 11 [IQR, 5] mm/sec [P = .004] and 6 [IQR, 3] to 9 [IQR, 6] mm/sec [P = .004], respectively). PLA rate of change during full expiration and change in PLA during tidal breathing improved (from a mean of 42 cm2/sec ± 16 to 56 cm2/sec ± 24 [P = .03] and from a mean of 29 cm2 ± 14 to 35 cm2 ± 10 [P = .03], respectively). Conclusion Dynamic chest radiography demonstrated improvement in diaphragm speed and range of chest wall movement during respiration aftere treatment for pulmonary exacerbations in cystic fibrosis and showed potential as a tool to investigate the effect of pulmonary exacerbations on lung mechanics. Clinical trials registration no. NCT01234567 Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Elexacaftor/Tezacaftor/Ivacaftor as a Bridge to Lung Retransplant in a Recipient With Cystic Fibrosis.

The triple-combination cystic fibrosis transmembrane conductance regulator modulator elexacaftor/- tezacaftor/ivacaftor is known to improve lung function and have extrapulmonary benefits in people with cystic fibrosis. However, there is limited evidence for its use in patients with cystic fibrosis after lung transplant, where the donor lung expresses normal levels of the cystic fibrosis transmembrane conductance regulator. We describe the use of elexacaftor/tezacaftor/ivacaftor as a bridge to potential lung retransplant in a 37-year-old man with cystic fibrosis and chronic lung allograft dysfunction. Although forced expiratory volume in 1 second did not improve, the patient had decreased sputum volume, no pulmonary exacerbations of cystic fibrosis, and no longer required continuous antibiotic therapy. Pancreatic function, revised Cystic Fibrosis Questionnaire scores, sinus symptoms, weight, and corticosteroid dependence significantly improved. There were no reported side effects attributable to elexacaftor/tezacaftor/ivacaftor. However, the patient exhibited declined renal function, which had been initially attributed to lability in cyclosporin levels but which were corrected after lithotripsy for renal calculi. Triple-combination modulators of the cystic fibrosis transmembrane conductance regulator may offer benefits to carefully selected individuals awaiting retransplant, balanced against the risk of worsened immunosuppressant level control.

Characterisation of hemidiaphragm dysfunction using dynamic chest radiography: a pilot study.

OBJECTIVES: Dynamic chest radiography (DCR) is a novel real-time digital fluoroscopic imaging system that produces clear, wide field-of-view diagnostic images of the thorax and diaphragm in motion, alongside novel metrics on moving structures within the thoracic cavity. We describe the use of DCR in the measurement of diaphragm motion in a pilot series of cases of suspected diaphragm dysfunction. METHODS: We studied 21 patients referred for assessment of diaphragm function due to suspicious clinical symptoms or imaging (breathlessness, orthopnoea, reduced exercise tolerance and/or an elevated hemidiaphragm on plain chest radiograph). All underwent DCR with voluntary sniff manoeuvres. RESULTS: Paradoxical motion on sniffing was observed in 14 patients, and confirmed in six who also underwent fluoroscopy or ultrasound. In four patients, DCR showed reduced hemidiaphragm excursion, but no paradoxical motion; in three, normal bilateral diaphragm motion was demonstrated. DCR was quick to perform, and well tolerated in all cases and with no adverse events reported. DCR was achieved in ∼5 min per patient, with images available to view by the clinician immediately within the clinical setting. CONCLUSION: DCR is a rapid, well-tolerated and straightforward chest radiography technique that warrants further investigation in the assessment of diaphragm dysfunction.

Unilateral diaphragm paralysis with COVID-19 infection.

Neurological complications are well described in SARS-CoV-2, but for the first time we report a case of unilateral diaphragm paralysis occurring early in mechanical ventilation for respiratory failure due to such an infection. The patient subsequently required tracheostomy and ventilator support for 37 days, and had increased breathlessness and an elevated diaphragm at clinic review 9 months later. Dynamic chest radiography demonstrated persistent diaphragm paralysis with an accompanying postural change in lung volumes, and he subsequently underwent surgical plication. This case demonstrates that although persistent dyspnoea is a common feature following SARS-CoV-2 infection and is usually due to deconditioning or persistent parenchymal involvement, it can be due to other causes and needs to be investigated appropriately.

Utility and validity of dynamic chest radiography in cystic fibrosis (dynamic CF): an observational, non-controlled, non-randomised, single-centre, prospective study.

INTRODUCTION: Dynamic chest radiography (DCR) uses novel, low-dose radiographic technology to capture images of the thoracic cavity while in motion. Pulmonary function testing is important in cystic fibrosis (CF). The tolerability, rapid acquisition and lower radiation and cost compared with CT imaging may make DCR a useful adjunct to current standards of care. METHODS AND ANALYSIS: This is an observational, non-controlled, non-randomised, single-centre, prospective study. This study is conducted at the Liverpool Heart and Chest Hospital (LHCH) adult CF unit. Participants are adults with CF. This study reviews DCR taken during routine CF Annual Review (n=150), validates DCR-derived lung volumes against whole body plethysmography (n=20) and examines DCR at the start and end of pulmonary exacerbations of CF (n=20). The primary objectives of this study are to examine if DCR provides lung function information that correlates with PFT, and lung volumes that correlate whole body plethysmography. ETHICS AND DISSEMINATION: This study has received the following approvals: HRA REC (11 December 2019) and LHCH R&I (11 October 2019). Results are made available to people with CF, the funders and other researchers. Processed, anonymised data are available from the research team on request. TRIAL REGISTRATION NUMBER: ISRCTN 64994816.