Prospective Detection of Early Lung Cancer in Patients With COPD in Regular Care by Electronic Nose Analysis of Exhaled Breath.

BACKGROUND: Patients with COPD are at high risk of lung cancer developing, but no validated predictive biomarkers have been reported to identify these patients. Molecular profiling of exhaled breath by electronic nose (eNose) technology may qualify for early detection of lung cancer in patients with COPD. RESEARCH QUESTION: Can eNose technology be used for prospective detection of early lung cancer in patients with COPD? STUDY DESIGN AND METHODS: BreathCloud is a real-world multicenter prospective follow-up study using diagnostic and monitoring visits in day-to-day clinical care of patients with a standardized diagnosis of asthma, COPD, or lung cancer. Breath profiles were collected at inclusion in duplicate by a metal-oxide semiconductor eNose positioned at the rear end of a pneumotachograph (SpiroNose; Breathomix). All patients with COPD were managed according to standard clinical care, and the incidence of clinically diagnosed lung cancer was prospectively monitored for 2 years. Data analysis involved advanced signal processing, ambient air correction, and statistics based on principal component (PC) analysis, linear discriminant analysis, and receiver operating characteristic analysis. RESULTS: Exhaled breath data from 682 patients with COPD and 211 patients with lung cancer were available. Thirty-seven patients with COPD (5.4%) demonstrated clinically manifest lung cancer within 2 years after inclusion. Principal components 1, 2, and 3 were significantly different between patients with COPD and those with lung cancer in both training and validation sets with areas under the receiver operating characteristic curve of 0.89 (95% CI, 0.83-0.95) and 0.86 (95% CI, 0.81-0.89). The same three PCs showed significant differences (P < .01) at baseline between patients with COPD who did and did not subsequently demonstrate lung cancer within 2 years, with a cross-validation value of 87% and an area under the receiver operating characteristic curve of 0.90 (95% CI, 0.84-0.95). INTERPRETATION: Exhaled breath analysis by eNose identified patients with COPD in whom lung cancer became clinically manifest within 2 years after inclusion. These results show that eNose assessment may detect early stages of lung cancer in patients with COPD.

Bronchial obstruction in osteogenesis imperfecta can be detected by forced oscillation technique.

Introduction: Respiratory insufficiency is a leading cause of death in individuals with osteogenesis imperfecta (OI). However, evaluating pulmonary function in OI presents challenges. Commonly used pulmonary function tests such as spirometry and body plethysmography are sometimes difficult to perform for OI patients, and reference intervals are not always applicable. The forced oscillation technique (FOT) is a patient-friendly method for detecting respiratory abnormalities that requires no effort from the patient. Objective: This study investigates the feasibility of FOT in the evaluation of respiratory function in the clinical management of OI patients. Methods: Twelve OI patients, comprising eight with Sillence OI I, two with OI IV, and two with OI III, underwent spirometry, body plethysmography, and FOT, both pre-and post-administration of salbutamol. Results: FOT measurements exhibited consistent trends that aligned with spirometry and body plethysmography findings. The resistance at 8 Hz decreased after the administration of salbutamol, indicating that FOT is able to detect bronchial obstruction and its alleviation by medication (p < 0.05). The resonant frequency during expiration was higher than during inspiration in nearly all patients, suggesting obstructive disease. The technique gives insight into both inspiratory and expiratory impairment of pulmonary ventilation. The main FOT parameters showed a relatively high repeatability in duplicate measurements. Conclusion: Bronchial obstruction can be detected by FOT in patients with OI during quiet breathing, making it an easily executable alternative to other lung function measurements. The technique can detect the bronchodilator effect of sympathomimetic medication. It has the potential to provide information on expiratory flow limitation, pulmonary restriction, and reduced lung compliance.

Deterioration of pulmonary function: An early complication in Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia Ossificans Progressiva (FOP) is a genetic disease characterized by the formation of heterotopic ossification (HO) in connective tissues. HO first develops in the thoracic region, before more peripheral sites are affected. Due to HO along the thoracic cage, its movements are restricted and pulmonary function deteriorates. Because development of HO is progressive, it is likely that pulmonary function deteriorates over time, but longitudinal data on pulmonary function in FOP are missing. Longitudinal pulmonary function tests (PFTs) from seven FOP patients were evaluated retrospectively to assess whether there were changes in pulmonary function during aging. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), total lung capacity (TLC), residual volume (RV) and diffusing lung capacity for carbon dioxide divided by alveolar volume (DLCO/VA) were included. In addition, HO volume along the thorax together with its progression as identified by whole body low dose CT scans were correlated to PFT data. Per patient, aged 7-57 years at the time of the first PFT, three to nine PFTs were available over a period of 6-18 years. Restrictive pulmonary function, identified by TLC or suspected by FVC, was found in all, but one, patients. In three patients, TLC, FVC or both decreased further during the follow-up period. All, but one, patients had an increased RV. The DLCO/VA ratio was normal in all FOP patients. Interestingly, FEV1 increased after a surgical intervention to unlock the jaw. In four out of five patients total HO volume in the thoracic region progressed beyond early adulthood, but no further decline in FVC was observed. In conclusion, restrictive pulmonary function was found in the majority of patients already at an early age. Our data suggest that the deterioration in pulmonary function is age dependent.

Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label.

Asthma and chronic obstructive pulmonary disease (COPD) are complex and overlapping diseases that include inflammatory phenotypes. Novel anti-eosinophilic/anti-neutrophilic strategies demand rapid inflammatory phenotyping, which might be accessible from exhaled breath.Our objective was to capture clinical/inflammatory phenotypes in patients with chronic airway disease using an electronic nose (eNose) in a training and validation set.This was a multicentre cross-sectional study in which exhaled breath from asthma and COPD patients (n=435; training n=321 and validation n=114) was analysed using eNose technology. Data analysis involved signal processing and statistics based on principal component analysis followed by unsupervised cluster analysis and supervised linear regression.Clustering based on eNose resulted in five significant combined asthma and COPD clusters that differed regarding ethnicity (p=0.01), systemic eosinophilia (p=0.02) and neutrophilia (p=0.03), body mass index (p=0.04), exhaled nitric oxide fraction (p<0.01), atopy (p<0.01) and exacerbation rate (p<0.01). Significant regression models were found for the prediction of eosinophilic (R2=0.581) and neutrophilic (R2=0.409) blood counts based on eNose. Similar clusters and regression results were obtained in the validation set.Phenotyping a combined sample of asthma and COPD patients using eNose provides validated clusters that are not determined by diagnosis, but rather by clinical/inflammatory characteristics. eNose identified systemic neutrophilia and/or eosinophilia in a dose-dependent manner.

Effects of diaphragm plication on pulmonary function and cardiopulmonary exercise parameters.

OBJECTIVES: Paralysis of the diaphragm is an uncommon condition, which may result in dyspnoea on excertion and in orthopnea. In patients who have symptoms, the paralysed diaphragm is often plicated to prevent its paradoxical movement on inspiration. This procedure brings relief to many patients, but the mechanism for this improvement is not well understood. METHODS: Nine symptomatic patients who underwent plication of a unilateral paralysed hemidiaphragm were prospectively evaluated. All patients underwent pulmonary function tests and cardiopulmonary exercise tests before surgery and repeated them after surgery. RESULTS: Patients with hemidiaphragm paralysis before surgery were found to have lower tidal volumes at any given ventilation rate during exercise than normal subjects. A clear and consistent change was found in the manner in which patients increased their ventilation during exercise after surgery. All patients showed an increase in tidal volume for a given ventilation rate, which was significant. The plication procedure reduced the respiratory rate for any exercise level in all patients, and this effect was more pronounced during exercise. CONCLUSIONS: In patients with hemidiaphragm paralysis who underwent a diaphragm plication exercise, tidal volumes increased and the ventilatory frequency decreased. Despite this improvement, maximal exercise capacity remained unaltered.

Smallest detectable change in volume differs between mass flow sensor and pneumotachograph.

BACKGROUND: To assess a pulmonary function change over time the mass flow sensor and the pneumotachograph are widely used in commercially available instruments. However, the smallest detectable change for both devices has never been compared. Therefore, the aim of this study is to determine the smallest detectable change in vital capacity (VC) and single-breath diffusion parameters measured by mass flow sensor and or pneumotachograph. METHOD: In 28 healthy pulmonary function technicians VC, transfer factor for carbon monoxide (DLCO) and alveolar volume (VA) was repeatedly (10×) measured. The smallest detectable change was calculated by 1.96 x Standard Error of Measurement ×√2. FINDINGS: The mean (range) of the smallest detectable change measured by mass flow sensor and pneumotachograph respectively, were for VC (in Liter): 0.53 (0.46-0.65); 0.25 (0.17-0.36) (p = 0.04), DLCO (in mmol*kPa-1*min-1): 1.53 (1.26-1.7); 1.18 (0.84-1.39) (p = 0.07), VA (in Liter): 0.66. (0.53-0.82); 0.43 (0.34-0.53) (p = 0.04) and DLCO/VA (in mmol*kPa-1*min-1*L-1): 0.22 (0.19-0.28); 0.19 (0.14-0.22) (p = 0.79). CONCLUSIONS: Smallest detectable significant change in VC and VA as measured by pneumotachograph are smaller than by mass flow sensor. Therefore, the pneumotachograph is the preferred instrument to estimate lung volume change over time in individual patients.