Background/Objectives: The prevalence of Achromobacter xylosoxidans is increasing in people with Cystic Fibrosis (pwCF), yet its clinical pathogenicity remains controversial. The objective of this study was to chart the longitudinal prevalence and examine clinical associations before and after infection. Methods: This observational, retrospective study was conducted at a single CF center over a 14-year period. Data were collated from patient charts and clinic databases. Patients with Achromobacter sputum cultures were compared to those without the bacterium and analyzed according to whether they had single, intermittent, or chronic infections. Results: During the study period, an annual average of 124 pwCF were followed up at our clinic, with a median age of 13.6 years (IQR = 7.6-27.7). The Achromobacter detection rate increased from 0 to 6.1%. Twenty-three percent (29/124) of patients had at least one positive culture. The median age at acquisition was 17 years (IQR = 14.5-33). At the time of acquisition, the median FEV1 was 81% (IQR = 46-94), compared to 90% (IQR = 72-99) for patients without Achromobacter, p < 0.001. Patients with Achromobacter tended to demonstrate more chronic Pseudomonas (55% vs. 27%, p = 0.06) and pancreatic insufficiency (66% vs. 47%, p = 0.07). At two years post-acquisition, the median FEV1 for patients with intermittent and chronically infected decreased by 11.5% (IQR = -3.75-7.5), compared to 1.5% (IQR = -2.5-12.5) for those with a single positive culture, p = 0.03. Similarly, pulmonary exacerbations per year became more frequent post-acquisition in intermittent and chronically infected patients: Median (range) 2.5 (0-8) pre-, versus 3.0 (0-9) post-acquisition, p = 0.036. Conclusions: Chronic and intermittent infection with Achromobacter were associated with accelerated lung function decline and increased exacerbation frequency. Larger prospective studies are needed to confirm these findings and examine the effect of eradication on the clinical course.

Background: Elevated immunoglobulin G (IgG) levels are associated with worse lung function and disease severity in people with cystic fibrosis (PwCF). This study evaluated whether elevated IgG levels-defined as values above the 97.5th percentile (Z-score ≥ 1.96 standard deviations above the mean)-can predict progression to severe lung disease. Methods: A retrospective cohort study of children and adults with CF at a single-center clinic was performed. Patients with elevated baseline IgG Z-scores were compared to those with normal or low IgG levels. Progression to severe lung disease was defined as % predicted FEV1 < 40%, referral for lung transplantation, or death. Kaplan-Meier survival curves and Cox models were used to analyze clinical outcomes. A sensitivity analysis was conducted for patients aged 18 years or older. Results: Of 97 patients, 31 (31.9%) had elevated IgG levels. Progression to severe lung disease occurred in 14 (14.4%) patients, 12 (85.7%) of whom had elevated IgG. These patients were significantly older and had a higher prevalence of Pseudomonas aeruginosa colonization. Among adults, those with elevated IgG had lower baseline % predicted FEV1 and greater annual lung function decline. Elevated IgG was independently associated with progression to severe lung disease (adjusted hazard ratio [aHR]: 9.8; 95% CI: 1.9-48.6), even after adjusting for Pseudomonas colonization and annual % predicted FEV1 decline. Conclusions: Elevated IgG was associated with progression to severe lung disease in PwCF and correlated with older age, Pseudomonas colonization, and-in adults-lower baseline lung function and faster decline. These findings highlight elevated serum IgG as a meaningful prognostic biomarker for identifying high-risk PwCF who may benefit from closer monitoring and earlier intervention.

BACKGROUND:Vaccines are a cornerstone of modern medicine, however, in some regions, low coverage is reported in patients with chronic diseases, including people with cystic fibrosis (pwCF), compared to the general population. METHODS:This retrospective multicenter study in Israel included pwCF born after January 1, 2000, and compared them to the general population. Vaccination data were collected from patient databases and the Ministry of Health reports for the general population. RESULTS:Out of 269 eligible pwCF aged 6 months to 23 years, a total of 173 were included. Coverage for the initial DTaP-IPV-HiB vaccine, administered in the first year of life, was similar between pwCF and the general population (92% compared with 96%, p = 0.23). In contrast, coverage for other routine vaccines given in the first year of life was significantly lower in pwCF: HAV (76% compared with 92%), HBV (85% compared with 96%), and the first dose of MMRV (85% compared with 97%) (all p < 0.001). Booster dose coverage for DTaP-IPV-HiB and MMRV, given at age 6-7 years, was also significantly reduced in pwCF (72% compared with 95% and 68% compared with 96% respectively, p < 0.001). Pneumococcal conjugate vaccine uptake was significantly lower in pwCF (61.8% vs. 94% in the general population p < 0.001), while the 23-valent pneumococcal vaccine was slightly more prevalent among pwCF compared to those with other chronic conditions, although uptake was low in both groups (15% vs. 10%, p = 0.001). Influenza vaccination rates during 3 seasons were significantly higher in pwCF (65%-70% vs. 20-27% in the general population, p < 0.001), whereas COVID-19 vaccine uptake was lower in adolescent pwCF compared to their general population peers (38.5% vs. 57.4%, p = 0.04). CONCLUSION:Our study highlights suboptimal vaccine coverage among pwCF, particularly after the first year of life, affecting both routine early-life vaccines and booster doses. Greater awareness and proactive measures are needed to ensure adequate vaccination.

Background: Although extremely premature birth disrupts lung development, adolescent survivors of extreme prematurity show good clinical and physiologic outcomes. Cardiopulmonary limitations may not be clinically evident at rest. Data regarding exercise limitation in adolescents following preterm birth in the postsurfactant era are limited.Research Question: What are the long-term effects of bronchopulmonary dysplasia (BPD) and extreme prematurity (<29 weeks) on ventilatory response during exercise in adolescents in the postsurfactant era?Study Design and Methods: We followed a longitudinally recruited cohort of children aged 13-19 years who were born at a gestational age of <29 weeks (study group - SG). We compared the cardiopulmonary exercise testing (CPET) results of those with and without BPD, to their own CPET results from elementary school age (mean 9.09 +/- 1.05 years).Results: Thirty-seven children aged 15.73 +/- 1.31 years, mean gestational age 26 weeks ( +/- 1.19), completed the study. CPET parameters in adolescence were within the normal range for age, including mean VO2 peak of 91% predicted. The BPD and non-BPD subgroups had similar results. In the longitudinal analysis of the SG, improvement was observed in adolescence, compared with elementary school age, in breathing reserve (36.37 +/- 18.99 vs. 26.58 +/- 17.92, p = 0.044), tidal volume as a fraction of vital capacity achieved at maximal load (0.51 +/- 0.13 vs. 0.37 +/- 0.08, p < 0.001), and respiratory exchange ratio at maximal load (1.18 +/- 0.13 vs. 1.11 +/- 0.10, p = 0.021).Interpretation: In the current cohort, adolescents born extremely premature have essentially normal ventilatory response during exercise, unrelated to BPD diagnosis. CPET results in this population improve over time.

Background: Lung function deterioration in cystic fibrosis (CF) is typically measured by a decline in the forced expiratory volume in one second (FEV1%), which is thought to be a late marker of lung disease. Dynamic hyperinflation (DH) is seen in obstructive lung diseases while exercising. Our aim was to assess whether DH could predict pulmonary deterioration in CF; a secondary measure was the peak VO2. Methods: A retrospective study was conducted of people with CF who performed cardiopulmonary exercise tests (CPETs) during 2012–2018. The tests were classified as those demonstrating DH non-DH. Demographic, genetic, and clinical data until 12.2022 were extracted from patient charts. Results: A total of 33 patients aged 10–61 years performed 41 valid CPETs with valid DH measurements; sixteen (39%) demonstrated DH. At the time of the CPETs, there was no difference in the FEV1% measurements between the DH and non-DH groups (median 83.5% vs. 87.6%, respectively; p = 0.174). The FEV1% trend over 4 years showed a decline in the DH group compared to the non-DH group (p = 0.009). A correlation was found between DH and the lung clearance index (LCI), as well as the FEV1% (r = 0.36 and p = 0.019 and r = −0.55 and p = 0.004, respectively). Intravenous (IV) antibiotic courses during the 4 years after the CPETs were significantly more frequent in the DH group (p = 0.046). The peak VO2 also correlated with the FEV1% and LCI (r = 0.36 and p = 0.02 and r = −0.46 and p = 0.014, respectively) as well as with the IV antibiotic courses (r = −0.46 and p = 0.014). Conclusions: In our cohort, the DH and peak VO2 were both associated with lung function deterioration and more frequent pulmonary exacerbations. DH may serve as a marker to predict pulmonary deterioration in people with CF.

The ancient Greeks took the entertainment of their crowds very seriously and used drama as a way of investigating the world they lived in. The theatrical re-enactment of suffering and grief in front of a large audience was to foster compassion, as well as a cathartic release of emotion that was restorative through a deeply felt interconnection between actors and audience. When our patients encounter tragedy, we are also drawn into their ordeal and experience it first hand. Such it was with Rose.

BACKGROUND:Cystic fibrosis (CF) is a chronic life-threatening disease. In patients who suffer from chronic disease, Attention Deficit Hyperactivity Disorder (ADHD) is associated with functional impairment that can affect adherence to treatment and consequently influence prognosis.METHODS:CF patients filled in the ADHD Rating Scale (ADHD-RS) adapted to the DSM5 and were assessed on a continuous performance task (MOXO-CPT), a standardized-computerized test designed to evaluate several domains of attention.RESULTS:Of the 175 patients (99 males), 18% presented ADHD symptoms, according to ADHD-RS; 16% in the younger group (<18years), and 18.9% in the adult group. The male to female ratio was 3:1 in children and 1:1 in adults.CONCLUSIONS:The occurrence of ADHD symptoms in patients with CF is substantially higher than in the general population and should be recognized as a co-morbidity of CF. As ADHD can impair adherence to therapy, further research is needed to investigate the effect of ADHD therapy on adherence.

BACKGROUND:Population genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features. METHODS:This was a retrospective national study. Demographic and clinical characteristics of children with CF born in Israel between 2008 and 2018 were obtained from the national CF registry and from patients' medical records. Data on CF births, preimplantation genetic testing (PGT), pregnancy termination and de-identified data from the PGCS program were collected. RESULTS:CF births per 100,000 live births decreased from 8.29 in 2008 to 0.54 in 2018 (IRR = 0.84, p < 0.001). The CF pregnancy termination rate did not change (IRR = 1, p=  0.9) while the CF-related PGT rate increased markedly (IRR = 1.33, p < 0.001). One hundred and two children were born with CF between 2008 and 2018 with a median age at diagnosis of 4.8 months, range 0-111 months. Unlike the generally high uptake nationally, 65/102 had not performed PGCS. Even if all had utilized PGCS, only 51 would have been detected by the existing genetic screening panel. Clinically, 34 % of children were pancreatic sufficient compared to 23 % before 2008 (p = 0.04). CONCLUSIONS:Since institution of a nationwide PGCS program, the birth of children with CF decreased markedly. Residual function variants and pancreatic sufficiency were more common. A broader genetic screening panel and increased PGCS utilization may further decrease the birth of children with CF.

Videofluoroscopy swallow studies (VFSS) are gold standard to diagnose aspiration in children but require resources and radiation compared with clinical feeding evaluation (CFE). We evaluated their added value for diagnosis, feeding management and clinical status. A retrospective single-centre cross-sectional study of children aged 0–18 years, with respiratory morbidity, referred for VFSS at a tertiary pediatric hospital. A total of 113 children, median age (range) 2.2 years (0.1–17.9), underwent VFSS. Diagnosis included chronic pulmonary aspiration (CPA), 87 (77%); neurological, 73 (64%); gastrointestinal, 73 (64%) and congenital heart disease, 42 (37%), not mutually exclusive. Forty-six (41%) aspirated, 9 (8%) only overtly and 37 (33%) including silent aspirations. Those with CPA or cerebral palsy were more likely to have VFSS aspiration, OR 3.2 and 9.8 respectively. Feeding recommendations after VFSS differed significantly from those based on prior CFE, p  < 0.001: The rate of exclusively orally fed children rose from 65% to 79%, p  = 0.006; exclusively enterally fed children from 10% to 14%; p  = 0.005. During the year after VFSS, there were significantly less antibiotic courses, total and respiratory admissions. In this population with high prevalence of clinically suspected CPA, VFSS altered feeding management compared with CFE and may have contributed to subsequent clinical improvement.

Background Video fluoroscopy swallow studies (VFSS) are considered gold standard for the diagnosis of aspiration in children but require resources and radiation compared to clinical feeding evaluation (CFE). We evaluated their added value for diagnosis, feeding management and clinical status. Methods A retrospective single-center cohort study of children aged 0-18 years, referred for VFSS at a tertiary pediatric hospital. Results 113 children, median age (range) 2.2 years (0.1-17.9) successfully completed VFSS. Forty-six (41%) had oropharyngeal aspiration, 9 (8%) overt alone and 37 (33%) including silent aspirations. Underlying medical conditions included clinically suspected aspiration lung disease (ALD), 87 (77%); neurologic disease, 73 (64%); gastrointestinal disease, 73 (64%) and congenital heart disease, 42 (37%), not mutually exclusive. Those with ALD or cerebral palsy were more likely to have aspiration by VFSS, OR 3.2 and 9.8 respectively. Sensitivity and specificity of CFE for VFSS diagnosis of aspiration were 71% and 84% respectively. Feeding recommendations after VFSS differed significantly from those based on prior CFE, p<0.001: The rate of exclusively orally fed children increased from 65% to 79%, p=0.006 and exclusively enterally fed children from 10% to 14%; p=0.005. During the following year, there were significantly less antibiotic courses, as well as total and respiratory admissions. Conclusions In this population of children with a high prevalence of clinically suspected ALD, VFSS refined diagnosis and altered feeding management compared to CFE, with subsequent clinical improvement.

Background: Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract disorder causing hospitalization in infants. Palivizumab has shifted the profile of the hospitalized population away from premature infants and towards those with chronic morbidities who are not eligible for prophylaxis. Aim: To characterize RSV bronchiolitis hospitalizations in infants with chronic diseases, compared to otherwise healthy infants. Methods: A four consecutive RSV season retrospective analysis of patients younger than two years admitted with bronchiolitis. Background demographic and clinical data, including vital sign measurements, laboratory tests, and pediatric intensive care unit (PICU) admissions during hospitalization, were analyzed. Results: Of 1124 hospitalizations due to RSV bronchiolitis, 244 (22%) were in infants with chronic diseases. Although 20/1124 qualified for RSV prophylaxis, only 8 had been vaccinated. Compared to otherwise healthy infants, children with chronic diseases had longer hospitalizations, median 4 days (IQR 4-7) vs 3 days (2-5), p<0.001; and higher PICU and readmission rates (9% vs 4.5%, p=0.007 and 3% vs 1%, p=0.055, respectively). Children with Down’s syndrome comprised 2% of all hospitalizations, but 8% of PICU admissions; their median length of hospitalization was 11 days. Respiratory tract malformations were present in 2% of hospitalizations, and comprised 4% of PICU admissions. Conclusion: Infants with chronic diseases admitted with RSV bronchiolitis are prone to longer hospitalization and PICU admission. Children with Down’s syndrome and respiratory tract malformations may benefit from RSV prophylaxis.

BACKGROUND:With increasing longevity and quality of life in adults with Cystic fibrosis (CF), growing maternity rates are reported. Women with severe CF are becoming pregnant, with unpredictable maternal and fetal outcomes.AIM:To determine how baseline disease severity, pancreatic insufficiency (PI) and Pseudomonas aeruginosa (PA) infection affect fertility, the pregnancy course, delivery, neonatal outcome, and subsequent disease progression.METHODS:A multicenter-retrospective cohort study. Data on patients that had been pregnant between 1986-2018 was collected from ten CF centers worldwide. Disease severity [mild or moderate-severe (mod-sev)] was defined according to forced expiratory volume % predicted in 1 second (FEV1) and body mass index (BMI). Three time periods were compared, 12 months prior to conception, the pregnancy itself and the 12 months thereafter.RESULTS:Data was available on 171 pregnancies in 128 patients aged 18-45 years; 55.1% with mod-sev disease, 43.1% with PI and 40.3% with PA. Women with mod-sev disease had more CF-related complications during and after pregnancy and delivered more preterm newborns. However, FEV1 and BMI decline were no different between the mild and mod-sev groups. A more rapid decline in FEV1 was observed during pregnancy in PI and PA infected patients, though stabilizing thereafter. PI was associated with increased risk for small for gestational age infants.CONCLUSION:Baseline disease severity, PA infection and PI have an adverse impact on infant outcomes, but do not impact significantly on disease progression during and after pregnancy. Consequently, pregnancies in severe CF patients can have a good prognosis.

Background Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract disorder causing hospitalization in infants. Due to decreased hospitalization rates of premature infants following Palivizumab immune prophylaxis, the proportion of infants with chronic diseases not eligible for Palivizumab has increased. Aim To characterize infants hospitalized during 2014-2018 with RSV bronchiolitis, to compare between those with and without chronic conditions, and to identify risk factors for severe disease. Methods This retrospective study analyzed demographic and clinical data of patients younger than 2 years admitted with bronchiolitis during four consecutive RSV seasons. Results Of 1124 hospitalizations due to RSV bronchiolitis, 244 (22%) were in infants with chronic diseases. Although 20/1124 qualified for RSV prophylaxis, only eight received immune prophylaxis. Compared to otherwise healthy infants, children with chronic diseases had longer hospitalizations, median 4.8 days (interquartile range [IQR]: 3.4-8.3) versus 3.7 days (IQR: 2.7-5.1), p < .001; and higher pediatric intensive care unit (PICU) and readmission rates (9% vs. 4.5%, p = .007% and 3% vs. 1%, p = .055, respectively). Children with Down's syndrome comprised 2% of all hospitalizations, but 8% of PICU admissions; their median length of hospitalization was 10.7 days (IQR: 6.6-17.6). Respiratory tract malformations were present in 2% of hospitalizations, and comprised 4% of PICU admissions. Conclusion Among infants admitted with RSV bronchiolitis, those with chronic diseases had longer hospitalizations and higher rates of transfer to the PICU. Children with multiple comorbidities, and especially those with Down's syndrome, are at particularly high risk for severe hospitalization and may benefit from RSV immune prophylaxis.

BACKGROUND Adherence to treatment by adolescents and adults with cystic fibrosis (CF) is often poor. OBJECTIVES To assess the impact of a focused clinical intervention on adherence in individual patients, including help in problem-solving key barriers to adherence. To implement a patient-centered problem-solving intervention using CF My Way tools. To identify and overcome a selected barrier to adherence. METHODS Medication possession ratios (MPRs), number of airway clearance sessions, forced expiratory volume (FEV1), body mass index (BMI), and health-related quality of life (HRQoL) were measured before and after the intervention. RESULTS Sixteen patients with CF, aged 23.4 ± 6.7 years, participated. MPR increased for colistimethate sodium and tobramycin inhalations from a median of 21 (range 0-100) to 56 (range 0-100), P = 0.04 and 20 (range 0-100) to 33.3 (range 25-100), P = 0.03, respectively. BMI standard deviation score rose from -0.37 to -0.21, P = 0.05. No significant improvements were found in FEV1, airway clearance, or HRQoL scores. CONCLUSIONS The CF My Way problem-solving intervention increased adherence to medical treatments by removing barriers directly related to the needs and goals of young adults with CF.

The 2019 novel coronavirus (SARS-CoV-2) is endangering human health worldwide; scarcity of published pediatric cases and current literature and the absence of evidence-based guidelines necessitate international sharing of experience and personal communication. On 31 March 2020 the International Committee of the American Thoracic Society Pediatrics Assembly recorded an online podcast, during which pediatric pulmonologists worldwide shared their experience on the novel coronavirus disease (COVID-19) in children. The aim was to share personal experience in organizing pediatric care in different health care settings globally, protecting health care workers, and isolation practices. This manuscript summarizes the common themes of the podcast which centered around three main topics: more benign clinical disease and progression in pediatric cases compared to adults, a strong need for strategies to protect health care workers, and social or economic disparities as a barrier to successful pandemic control.

BACKGROUND:Acquiring sputum cultures from infants is considered challenging. We describe their yield in infants with cystic fibrosis (CF) and other chronic suppurative lung diseases (CSLDs). METHODS:Retrospective medical record review over a 4-year period, for infants aged 0-2 years with ≥2 airway bacterial cultures acquired by deep suction or induced sputum ≥4 weeks apart. Data included demographics, culture results, and clinical status. RESULTS:A total of 98 infants (16 CF) were evaluated and 534 sputum cultures acquired, 201 in CF and 333 in CSLD. There were 12 (2-23), median (range) cultures/CF infant, and 3 (2-21)/CSLD infant. Age at first culture was 3.8 (1-19.5) months for CF and 10.4 (0.5-22) months for CSLD; p = .016. In total, 360 cultures (67%) were positive for any bacteria, with 170/234 (73%) positive during exacerbations, compared with 190/300 (63%) during routine visits; p = .05. More infants with CF than CSLD had cultures positive for Staphylococcus aureus (SA; 75% vs. 34%; p = .004) throughout the period. Pseudomonas aeruginosa (PA) was common in both CF and CSLD (56% and 44%, respectively; p = .42) and increased over time for CF but was high throughout for CSLD. The number of hospital days before PA acquisition was 6 (10.2) for CF and 28.8 (38.7) for CSLD (p = .003). No CF but 6/82 (7%) CSLD infants had chronic PA (p = .56). CONCLUSIONS:Sputum cultures showed that infection, in particular PA, is common in CF and CSLD whereas SA is more common in CF. Prospective studies are warranted to elucidate the role of active surveillance in guiding antibiotic therapy.

BACKGROUND: Prematurity is a risk factor for impaired lung function. We sought to assess the long-term effect of palivizumab immunization and extreme prematurity (<29 weeks gestation) on respiratory symptoms and pulmonary function in adolescence. RESEARCH QUESTION: What is the long-term effect of palivizumab immunization and extreme prematurity (<29 weeks) on respiratory symptoms and pulmonary function in adolescence? STUDY DESIGN AND METHODS: We examined survivors of extreme prematurity (<29 weeks gestation) at 13 to 18 years of age (study group). Study group babies who were born immediately before palivizumab immunization (nonpalivizumab group [NPG]) were compared with those babies who were born just after implementation (PG) and with a control group. For study group patients, lung function in adolescence was further compared longitudinally with that at primary school age. RESULTS: Sixty-four adolescents aged 15.76 +/- 1.52 years were included: 46 in the study group (17 PG and 29 NPG) and 18 in the control group. For the study group, wheezing episodes, inhaler use, and hospitalizations were uncommon. For the study group compared with the control group, FEV1 percent predicted was 82.60% +/- 13.54% vs 105.83% +/- 13.12% (P < .001), and the lung clearance index was 7.67 +/- 1.02 vs 7.46 +/- 0.70 (P = .48), respectively. Study group adolescents with bronchopulmonary dysplasia had a higher lung clearance index than did adolescents with no bronchopulmonary dysplasia (7.94 +/- 1.11 vs 7.20 +/- 0.60; P = .002). PG and NPG adolescents were not significantly different. Comparing the study group in adolescence with primary school age, we found improvement in mean FEV1 percent predicted bronchodilator response (0.37% +/- 9.98% vs 5.67% +/- 9.87%; P = .036) and mean provocative concentration causing 20% decline in FEV1 (12.16 +/- 4.71 mg/mL vs 4.14 +/- 4.51 mg/mL, respectively; P < .001). INTERPRETATION: Palivizumab did not provide any discernable long-term protective effect. Nevertheless, adolescent survivors of extreme prematurity showed good clinical and physiologic outcomes, except for mildly raised lung clearance index in patients with bronchopulmonary dysplasia. Airway hyperreactivity detected at primary school age, decreased by adolescence.