Pulmonary exacerbations, airway pathogens, and long-term course of lung clearance index in children and young adults with cystic fibrosis.

BACKGROUND: Pulmonary exacerbations (PEx), pathogens colonizing the respiratory tract, and patients' age are associated with progressive worsening of lung function among patients with cystic fibrosis (CF). However, the effect of these factors on longitudinal changes of Lung Clearance Index (LCI) remains unclear. AIM: To assess the role of age, different types of bronchial infection, and PEx on LCI deterioration. METHODS: We conducted a retrospective study assessing multiple-breath washout (MBW) and spirometry changes among CF patients evaluated at quarterly outpatient clinic visits over 8 years. MBW and spirometry were performed at each visit, sputum samples and/or cough swabs were obtained for culture, whereas respiratory symptoms and clinical examination findings were recorded. Patients who had ≥5 serial MBW measurements, one of which coincided with a pulmonary exacerbation, were reviewed. RESULTS: Seventy-six patients were included in the study: mean age of 10.61 years (range 1.75-23.75). A total of 1152 MBW tests and 1047 spirometry tests were performed. LCI was significantly higher among CF patients aged 11-15, 16-20, and over 20 years than those under 5 years of age; ΔLCI: 1.16 (confidence interval [CI] 0.43-1.90) and 3.25 (CI 2.33-4.17), respectively. Furthermore, LCI was significantly elevated in CF patients with positive cultures for Pseudomonas aeruginosa (0.52 LCI [CI -0.12 to 0.71]) and Stenotrophomonas Maltophilia (1.41 LCI [CI 0.61-2.21]). Moreover, increased values of LCI in CF patients were significantly associated with increased risk of PEx (odds ratio [OR] 1.19, CI [1.14-1.25], p < 0.001). CONCLUSION: LCI demonstrates a progression of lung disease and corresponds to changes in bacterial infections and PEx among patients with CF. LCI may be a valuable marker for tracking disease deterioration and may have a role in the routine clinical care of patients with CF.

The Fitter the Better? Cardiopulmonary Exercise Testing Can Predict Pulmonary Exacerbations in Cystic Fibrosis.

BACKGROUND: The role of cardiopulmonary exercise testing (CPET) in the assessment of prognosis in CF (cystic fibrosis) is crucial. However, as the overall survival of the disease becomes better, the need for examinations that can predict pulmonary exacerbations (PEx) and subsequent deterioration becomes evident. METHODS: Data from a 10-year follow up with CPET and spirometry of CF patients were used to evaluate whether CPET-derived parameters can be used as prognostic indexes for pulmonary exacerbations in patients with CF. Pulmonary exacerbations were recorded. We used a survival analysis through Cox Regression to assess the prognostic role of CPET parameters for PeX. CPET parameters and other variables such as sputum culture, age, and spirometry measurements were tested via multivariate cox models. RESULTS: During a 10-year period (2009-2019), 78 CF patients underwent CPET. Cox regression analysis revealed that VO2peak% (peak Oxygen Uptake predicted %) predicted (hazard ratio (HR), 0.988 (0.975, 1.000) p = 0.042) and PetCO2 (end-tidal CO2 at peak exercise) (HR 0.948 (0.913, 0.984) p = 0.005), while VE/VO2 and (respiratory equivalent for oxygen at peak exercise) (HR 1.032 (1.003, 1.062) p = 0.033) were significant predictors of pulmonary exacerbations in the short term after the CPET. Additionally, patients with VO2peak% predicted <60% had 4.5-times higher relative risk of having a PEx than those with higher exercise capacity. CONCLUSIONS: CPET can provide valuable information regarding upcoming pulmonary exacerbation in CF. Patients with VO2peak <60% are at great risk of subsequent deterioration. Regular follow up of CF patients with exercise testing can highlight their clinical image and direct therapeutic interventions.

Change in CF care during COVID-19 pandemic: Single-center experience in a middle-income setting.

INTRODUCTION: The coronavirus 2019 (COVID-19) pandemic has demanded care changes for patients with chronic disease. Patients with cystic fibrosis (CF) are considered at higher risk of developing severe manifestations in the case of SARS-CoV-2 infection, and a need for new ways of safer care delivery has been required to avoid transmission. OBJECTIVES: To assess the impact of the lockdown during the first wave of the COVID-19 pandemic and remote monitoring on patient's health status and daily maintenance therapy in a middle-income resource setting. METHODS: During the first wave of the pandemic period, we changed from regular clinic visits to telephone visit calls to monitor our patients' health condition and adherence to physiotherapy and physical exercise. RESULTS: A total of 120 patients or their caregivers have been contacted by telephone call visits over 10 weeks. During this period, 38 patients (28.33%) were identified to have pulmonary exacerbation; 89.5% were prescribed oral antibiotics, 3% were hospitalized to get iv antibiotics, and 8% of the patients presented other CF complications. Most of the patients did not change the frequency of the daily physiotherapy. Moreover, 71% of the patients who performed regular physical exercise changed the frequency and the type of exercise during the quarantine period. Interestingly, mean forced expiratory volume in 1 s and body weight increased significantly and after the lockdown period. CONCLUSIONS: During the COVID-19 pandemic, the implementation of telephone contact processes aiming for CF patients' appropriate care is of great importance. Further studies are needed to evaluate patient outcomes when transitioning from face-to-face clinics to telemedicine clinics.

Toward the Establishment of New Clinical Endpoints for Cystic Fibrosis: The Role of Lung Clearance Index and Cardiopulmonary Exercise Testing.

As Cystic Fibrosis (CF) treatment advances, research evidence has highlighted the value and applicability of Lung Clearance Index and Cardiopulmonary Exercise Testing as endpoints for clinical trials. In the context of these new endpoints for CF trials, we have explored the use of these two test outcomes for routine CF care. In this review we have presented the use of these methods in assessing disease severity, disease progression, and the efficacy of new interventions with considerations for future research.

Ventilation efficiency to exercise in patients with cystic fibrosis.

INTRODUCTION: Exercise ventilation efficiency index in cardiopulmonary exercise testing (CPET) is elevated in patients with heart failure providing useful information on disease progression and prognosis. Few data, however, exist for ventilation efficiency index among cystic fibrosis (CF) patients. AIMS: To assess ventilation efficiency index (ΔVE/ΔVCO2 or V'E/V'CO2 slope) and intercept of ventilation (VE-intercept) in CF patients with mild, moderate, and severe cystic fibrosis (CF) lung disease. To assess possible correlations with ventilation inhomogeneity and structural damages as seen on high resolution computed tomography (HRCT). METHODS: CF patients with mild (FEV1 > 80%, n = 47), moderate (60% < FEV1 < 80%, n = 21), and severe (FEV1 < 60%, n = 9) lung disease, mean age 14.9 years participated. Peak oxygen uptake (VO2 peak), pulmonary ventilation at peak exercise (VE), respiratory equivalent ratios for oxygen and carbon dioxide at peak exercise (VE/VO2 , VE/VCO2 ), end-tidal CO2 (PetCO2 ), and ΔVE/ΔVCO2 , ΔVE/ΔVO2 in a maximal CPET along with spirometry and multiple breath washout indices were examined. HRCT scans were performed and scored using Bhalla score. RESULTS: Mean ΔVE/ΔVCO2 showed no significant differences among the three groups (P = .503). Mean VEint discriminated significantly among the different groups (p 2 < 0.001). Ventilation efficiency index did not correlate either with LCI or Bhalla score. However, VE together with ΔVE/ΔVCO2 slope could predict Bhalla score (r 2 = 0.869, P = .006). CONCLUSION: No significant differences were found regarding ΔVE/ΔVCO2 slope levels between the three groups. Ventilation intercept (VEint ) was elevated significantly as disease progresses reflecting increased dead space ventilation. CF patients retain their ventilation efficiency to exercise even as lung function deteriorates by adopting a higher respiratory rate along with increased dead space ventilation.

Predictive Value of 99MTC-hynic-toc Scintigraphy in Lung Neuroendocrine Tumor Diagnosis.

BACKGROUND: Νeuroendocrine tumors of the lungs are rare arising in the thymus and gastro-entero-pancreatic tract and belonging to foregut of neuroendocrine tumors. The aim of the present prospective study was to estimate the potential impact of single-photon emission computed tomography somatostatin receptor scintigraphy using 99mTc-Tektrotyd on diagnosis, treatment response, and prognosis in patients with neuroendocrine tumors of the lungs. METHODS: Thirty-six patients with neuroendocrine tumors of the lungs were evaluated by using 99mTc-HYNIC-TOC scintigraphy. The scintigraphic results were compared to liver tissue uptake (Krenning score). Likewise, the functional imaging results were compared with biochemical indices including chromogranin A, neuroendocrine-specific enolase, and insulin-like growth factor 1 at the time of diagnosis (baseline) and disease progression. RESULTS: The number of somatostatin receptors, expressed with Krenning score, did not show any correlation with the survival of patients both at baseline ( P = .08) and at disease progression ( P = .24), and scintigraphy results did not relate significantly to progression-free survival. Comparing the results of 99mTc-HYNIC-TOC scintigraphy according to the response of patients in the initial treatment, a statistically significant negative correlation was observed both in the first and in the second scintigraphy with patients' response ( P = .001 and P < .001, respectively). The concentrations of biochemical markers were in accordance with scintigraphy results in the diagnosis. CONCLUSION: This study indicates that 99mTc-HYNIC-TOC scintigraphy appears to be a reliable, noninvasive technique for detection of primary neuroendocrine tumors and their locoregional or distant metastases, although it cannot be used as a neuroendocrine tumors of the lungs predictive technique.

Does Pseudomonas aeruginosa Colonization Affect Exercise Capacity in CF?

INTRODUCTION: Cardio-Pulmonary Exercise Testing (CPET) has been recognized as a valuable method in assessing disease burden and exercise capacity among CF patients. AIM: To evaluate whether Pseudomonas aeruginosa colonization status affects Exercise Capacity, LCI and High-Resolution Computed Tomography (HRCT) indices among patients with CF; to check if Pseudomonas colonization can predict exercise intolerance. SUBJECTS: Seventy-eight (78) children and adults with CF (31 males) mean (range) age 17.08 (6.75; 24.25) performed spirometry, Multiple Breath Washout (MBW) and CPET along with HRCT on the same day during their admission or follow up visit. RESULTS: 78 CF patients (mean FEV1: 83.3% mean LCI: 10.9 and mean VO2 peak: 79.1%) were evaluated: 33 were chronically colonized with Pseudomonas aeruginosa, 24 were intermittently colonized whereas 21 were Pseudomonas free. Statistically significant differences were observed among the three groups in: peak oxygen uptake % predicted (VO2 peak% (p < 0.001), LCI (p < 0.001), as well as FEV1% (p < 0.001) and FVC% (p < 0.001). Pseudomonas colonization could predict VO2 peak% (p < 0.001, r 2: -0.395). CONCLUSION: Exercise capacity as reflected by peak oxygen uptake is reduced in Pseudomonas colonized patients and reflects lung structural damages as shown on HRCT. Pseudomonas colonization could predict exercise limitation among CF patients.

Lung clearance index (LCI) as a predictor of exercise limitation among CF patients.

INTRODUCTION: FEV1 is often considered the gold standard to monitor lung disease in cystic fibrosis (CF). Recently, there has been increasing interest in multiple breath washout (MBW) and cardiopulmonary exercise testing (CPET) as alternative or even more sensitive techniques. However, limited data exist on associations among the above methods. AIM: To evaluate the correlations between outcome measures of MBW and CPET and to examine if ventilation inhomogeneity can predict exercise intolerance. SUBJECTS AND METHODS: Ninety-seven children and adults with CF (47 males, mean [range] age 14.9 (6.6; 26.7) years, mean FEV1 : 90.8% predicted, mean lung clearance index [LCI]: 11.4, and mean peak oxygen uptake [VO2 peak]: 82.4% predicted) performed spirometry, MBW, and CPET on the same day during their admission or outpatient visit. RESULTS: LCI, m1 /m0 , and m2 /m0 (P < 0.001) as well as VO2 peak%, breathing reserve (BR), minute ventilation (VE)/VO2 (P < 0.001), and VE/carbon dioxide release (VCO2 ) (P = 0.006) correlated significantly with FEV1 %. LCI, m1 /m0 , and m2 /m0 correlated with VO2 peak (P ≤ 0.001), VE (L/min) (P < 0.05), BR (P < 0.01), VE/VO2 (P < 0.001), and VE/VCO2 (P < 0.01). Multiple regression analysis showed that LCI could predict BR% (P < 0.001, r2 :0.272) and VE/VO2 (P < 0.001, r2 : 0.207) while LCI and FRC could predict VO2 peak% P < 0.001, r2 : 0.216) and VE/VCO2 (P < 0.001, r2 : 0.226). CONCLUSION: Ventilation inhomogeneity as indicated by increased LCI is associated with less efficient ventilation during strenuous exercise and negatively impacts exercise capacity in CF.

A "real-life" study on height in prepubertal asthmatic children receiving inhaled steroids.

INTRODUCTION: Asthma is the most common chronic respiratory disease in children and inhaled corticosteroids (ICS) constitute the first line of treatment for these patients. However, the potential growth-inhibiting effect of ICS has often been a cause of concern for both caregivers as well as physicians, and there still remains conflict regarding their safety profile. OBJECTIVE: To assess whether the administration of ICS in low or medium doses is associated with height reduction in prepubertal children. METHODS: We performed a retrospective study to examine the association between ICS treatment and growth deceleration in children with mild persistent asthma. The comparison of height measurements every 6 months from 3 to 8 years of age was conducted among three groups of patients: patients not receiving ICS, patients being treated with low dose of ICS and patients being treated with medium dose of ICS (GINA Guidelines 2015). RESULTS: This study included 284 patients (198 male, 86 female) aged 3-8 years; 75 patients were not receiving ICS, 63 patients were on low-dose ICS and 146 patients were on medium-dose ICS. The measured height every 6 months did not differ significantly (p > 0.05) among the three groups while the difference remained stable (p > 0.05), even when we evaluated males and females separately. CONCLUSIONS: In this "real-life" study we found that long-term treatment with ICS in low or medium doses is not associated with height reduction in prepubertal children with asthma.

Exercise responses are related to structural lung damage in CF pulmonary disease.

INTRODUCTION: Early detection of lung disease is a primary objective in monitoring patients with Cystic Fibrosis (CF); High-Resolution-Computed-Tomography (HRCT) assesses structural damage. Spirometry and cardiopulmonary exercise testing are used for functional evaluation of CF lung disease. AIM: To evaluate the deterioration of exercise testing parameters over a 2-year period compared to the change of spirometry and HRCT parameters among CF patients. METHODS: Twenty-eight CF patients were evaluated with HRCT, spirometry, and exercise testing; 15 had two assessments with an interval of 2 years. Correlation analyses between Bhalla score parameters and functional measures were performed. RESULTS: Twenty-eight patients with CF (mean age 14.9 years, mean forced expiratory volume in 1 sec [FEV1 ] 83.2%) were evaluated. FEV1 was not found to change significantly in the 2-year period (P = 0.612). Both mean Bhalla score and mean peak oxygen consumption (VO2 peak %) deteriorated significantly (P = 0.014 and P = 0.026, respectively). VO2 peak and respiratory equivalents for O2 and CO2 at peak exercise were found to be significant predictors of Bhalla score (r = -0.477, P = 0.010; r = 0.461, P = 0.018; r = 0.402; P = 0.042, respectively). Anaerobic threshold was associated with changes in Bhalla score over the following 2 years. CONCLUSIONS: Exercise testing is more sensitive than spirometry to detect structural changes in CF lungs. Pediatr Pulmonol. 2016; 51:914-920. © 2016 Wiley Periodicals, Inc.