Standards for the care of people with cystic fibrosis; establishing and maintaining health.

This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.

Screening for Cystic Fibrosis Related Complications in the Context of a Pandemic and Altered Models of Care.

Background: Standard of care recommend that patients with cystic fibrosis (CF) require screening investigations to assess for complications. Changing models of care due to the COVID19 pandemic may have impacted completion of recommended screening. Objective: To compare the frequency of screening investigations completed in people with CF before and after the onset of the COVID19 pandemic. Methods: Medical records were reviewed at 4 CF-specialist centers to identify screening investigations completed in the 12-months before and after pandemic onset. Results: Records of 625 patients were reviewed. Prior to pandemic onset, there was between center variability in completion of screening investigations. There was greatest baseline variation between centers in performing oral glucose tolerance test (OGTT); range 38%-69%, exercise tests; 3%-51% and sputum screening for non-tuberculous mycobacteria; 53%-81%. Following pandemic onset, blood tests, and sputum cultures were maintained at the highest rates. Exercise testing, CXR and OGTT exhibited the greatest declines, with reductions at individual centers ranging between 10%-24%, 22%-43%, and 20%-26%, respectively. Return to in-person visits following pandemic onset was variable, ranging from 16% to 74% between centers. Conclusion: Completion of screening investigations varies between CF centers and changes in models of care, such as increased virtual care in response to COVID19 pandemic was associated with reduction in completion of investigations. Centers would benefit from auditing their adherence to standards of care, particularly considering recent changes in care delivery.

Diet and the gut-lung axis in cystic fibrosis - direct & indirect links.

Cystic fibrosis (CF) is a multisystem, autosomal, recessive disease primarily affecting the lungs, pancreas, gastrointestinal tract, and liver. Whilst there is increasing evidence of a microbial 'gut-lung axis' in chronic respiratory conditions, there has been limited analysis of such a concept in CF. We performed a comprehensive dietary and microbiota analysis to explore the interactions between diet, gastrointestinal microbiota, respiratory microbiota, and clinical outcomes in children with CF. Our results demonstrate significant alterations in intestinal inflammation and respiratory and gastrointestinal microbiota when compared to age and gender matched children without CF. We identified correlations between the gastrointestinal and respiratory microbiota, lung function, CF pulmonary exacerbations and anthropometrics, supporting the concept of an altered gut-lung axis in children with CF. We also identified significant differences in dietary quality with CF children consuming greater relative proportions of total, saturated and trans fats, and less relative proportions of carbohydrates, wholegrains, fiber, insoluble fiber, starch, and resistant starch. Our findings position the CF diet as a potential modulator in gastrointestinal inflammation and the proposed gut-lung axial relationship in CF. The dietary intake of wholegrains, fiber and resistant starch may be protective against intestinal inflammation and should be explored as potential therapeutic adjuvants for children with CF.

Procedural Pain Management During Tenotomy for Congenital Talipes Equinovarus.

The majority of infants with congenital talipes equinovarus (CTEV) require tenotomy of the tendoachilles. The pain response of this procedure in the awake infant has not been previously reported. In this observational study, multimodal pain management strategies, including oral sucrose, oral paracetamol, topical anesthetic, local anesthetic, a pacifier (dummy), and swaddling, were used. Physiological responses and pain were recorded. Pain was rated out of 10 at regular intervals, using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. Ninety-one infants (65 men, mean age = 53 days, range = 19-217 days) were observed. At baseline, median FLACC, heart rate (HR), and oxygen saturation (Spo2) were 1, 159, and 97% respectively. Peak median FLACC and HR were 9 and 200, respectively, and lowest median Spo2 was 92%. The median (interquartile range) time for FLACC to return to 3 or less was 2 (2-5) minutes. Achilles tenotomy for CTEV in the awake infant is associated with high pain levels despite provision of multimodal pain relief measures.

Clinical outcomes of adults and children with cystic fibrosis during the COVID-19 pandemic.

BACKGROUND: The onset of the COVID-19 pandemic was associated with restricted community movement and limited access to healthcare facilities, resulting in changed clinical service delivery to people with cystic fibrosis (CF). This study aimed to determine clinical outcomes of Australian adults and children with CF in the 12-months following the onset of the COVID-19 pandemic. METHODS: This longitudinal cohort study used national registry data. Primary outcomes were 12-month change in percent predicted forced expiratory volume in one second (FEV1 %pred), body mass index (BMI) in adults and BMI z-scores in children. A piecewise linear mixed-effects model was used to determine trends in outcomes before and after pandemic onset. RESULTS: Data were available for 3662 individuals (median age 19.6 years, range 0-82). When trends in outcomes before and after pandemic onset were compared; FEV1 %pred went from a mean annual decline of -0.13% (95%CI -0.36 to 0.11) to a mean improvement of 1.76% (95%CI 1.46-2.05). Annual trend in BMI improved from 0.03 kg/m2 (95%CI -0.02-0.08) to 0.30 kg/m2 (95%CI 0.25-0.45) and BMI z-scores improved from 0.05 (95%CI 0.03-0.07) to 0.12 (95%CI 0.09-0.14). Number of hospitalisations decreased from a total of 2656 to 1957 (p < 0.01). Virtual consultations increased from 8% to 47% and average number of consultations per patient increased from median (IQR) of 4(2-5) to 5(3-6) (p < 0.01). CONCLUSION: In the 12-months following the onset of the COVID-19 pandemic, there was an improvement in the clinical outcomes of people with CF when compared to the pre-pandemic period.

Telehealth application of an ultrasonic home spirometer.

OBJECTIVE: To investigate the validity and home use of a personal ultrasonic spirometer. METHODS: Supervised spirometry was performed using laboratory equipment and a personal ultrasonic spirometer. In addition, the ability of children to perform acceptable spirometry during supervised telehealth appointments at home was assessed. RESULTS: 59 children completed spirometry on both devices. There was high between-device intraclass correlation coefficient (ICC) for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC): ICC 0.991 (95% CI 0.985 to 0.995) and 0.989 (95% CI 0.981 to 0.993), respectively. Bland-Altman analysis revealed mean bias and limits of agreement of -0.01 (-0.22 to 0.24) L for FEV1 and -0.02 (-0.30 to 0.33) L for FVC. 125 of 140 (89%) supervised telehealth spirometry sessions were acceptable. CONCLUSION: There was excellent reliability in between-device measurements; however, the limits of agreement were wide. Therefore, caution is needed if the device is used interchangeably with laboratory equipment. High success rates of telehealth spirometry sessions indicate the device is suitable for this application.

Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research programme: a protocol for prospective, longitudinal, controlled, observational studies in children with chronic disease at an Australian tertiary paediatric hospital.

INTRODUCTION: Chronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the 'Evaluating the Alimentary and Respiratory Tracts in Health and disease' (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions. METHODS AND ANALYSIS: The EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of individual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts.Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor. ETHICS AND DISSEMINATION: Ethics approval: Sydney Children's Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04071314.

Children with bronchiectasis have poorer lung function than those with cystic fibrosis and do not receive the same standard of care.

BACKGROUND: Children with cystic fibrosis (CF) are routinely managed in a multidisciplinary clinic at tertiary pediatric centers. However, children with bronchiectasis may not be managed in the same way. We sought to compare the management model and clinical outcomes of children with bronchiectasis with children diagnosed with CF, in a single pediatric center. METHODS: We identified patients with bronchiectasis from hospital medical records at an urban tertiary pediatric hospital and identified a sex- and age-matched CF patient at the same center to compare lung function, nutritional status, frequency of physiotherapy and respiratory physician visits, and number of microbiological samples taken for bacterial culture. RESULTS: Twenty-two children with bronchiectasis were identified, mean (standard deviation [SD]) age was 11 (3) years. The most common known etiology for bronchiectasis was postinfective (6 of 22) but was unknown in 8 of 22. The cohort with bronchiectasis had poorer lung function (FEV1 mean [SD] percent predicted 78.6 [20.5] vs 94.5 [14.7], P = .005) and had less outpatient reviews by the respiratory physician (P < .001) and respiratory physiotherapist (P < .001) when compared to those with CF. Nutritional parameters did not differ between the groups. Many children (10 of 22, 45%) with bronchiectasis did not have any microbiological respiratory tract samples taken for evaluation. CONCLUSION: Children with bronchiectasis at this institution have poorer lung function than children with CF, and are deserving of improved multidisciplinary care.

Distress during airway sampling in children with cystic fibrosis.

BACKGROUND: Oropharyngeal suction and oropharyngeal swab are two methods of obtaining airway samples with similar diagnostic accuracy in children with cystic fibrosis (CF). The primary aim was comparing distress between suctioning and swabbing. A secondary aim was establishing the reliability of the Groningen Distress Rating Scale (GDRS). METHODS: Randomised oropharyngeal suction or swab occurred over two visits. Two physiotherapists and the child's parent rated distress using the GDRS. Heart rate (HR) was also measured. RESULTS: 24 children with CF, mean age of 3 years, participated. Both physiotherapist and parent rating showed significantly higher distress levels during suction than swab. Inter-rater reliability for the GDRS was very good between physiotherapists, and good between physiotherapist and parents. CONCLUSION: The study found that oropharyngeal swab is less distressing in obtaining samples than oropharyngeal suction and that the GDRS was reliable and valid.

Changing respiratory expectations with the new disease trajectory of nusinersen treated spinal muscular atrophy [SMA] type 1.

Spinal muscular atrophy [SMA] is the most common genetic cause of childhood mortality, primarily from the most severe form SMA type 1. It is a severe, progressive motor neurone disease, affecting the lower brainstem nuclei and the spinal cord. There is a graded level of severity with SMA children from a practical viewpoint described as "Non-sitters", "Sitters" and less commonly, "Ambulant" correlating with SMA Type 0/Type 1, Type 2 and Type 3 respectively. Children with SMA Type 0 have a severe neonatal form whilst those with SMA Type 1 develop hypoventilation, pulmonary aspiration, recurrent lower respiratory tract infections, dysphagia and failure to thrive before usually succumbing to respiratory failure and death before the age of 2 years. The recent introduction of the antisense oligonucleotide nusinersen into clinical practice in certain countries, following limited trials of less than two years duration, has altered the treatment landscape and improved the outlook considerably for SMN1 related SMA. Approximately 70% of infants appear to have a clinically significant response to nusinersen with improved motor function. It appears the earlier the treatment is initiated the better the response. There are other rarer genetic forms of SMA that are not treated with nusinersen. Clinical expectations will change although it is unclear as yet what the extent of response will mean in terms of screening initiatives [e.g., newborn screening], "preventative strategies" to maintain respiratory wellbeing, timing of introduction of respiratory supports, and prolonged life expectancy for the subcategory of children with treated SMA type 1. This article provides a review of the strategies available for supporting children with respiratory complications of SMA, with a particular emphasis on SMA Type 1.

Teaching Manually Assisted Cough to Caregivers of Children With Neuromuscular Disease.

BACKGROUND: Cough augmentation techniques are taught by health-care providers to improve secretion clearance and to help prevent respiratory infections in children with neuromuscular disease. There is some evidence of the effectiveness of a manually assisted cough when applied by health-care providers. However, it is unknown whether parents and caregivers may also be effective in applying manually assisted cough. The aim of this study was to evaluate whether parents and caregivers are effective at applying a manually assisted cough to a child with neuromuscular disease after being taught by a health-care provider. METHODS: For this prospective cohort study, children and their parents or caregivers were recruited from neuromuscular clinics in the Sydney Children's Hospitals Network. Cough peak flow was the outcome measure for the strength of the child's cough. Children were eligible to participate if their unassisted cough peak flow at baseline was <270 L/min. Parents and caregivers were taught a manually assisted cough by a physiotherapist before being measured. The cough peak flow was measured in the following order: (1) during an unassisted cough as baseline, (2) during a manually assisted cough performed by a physiotherapist, (3) during a manually assisted cough performed by a parent or caregiver, and (4) during an unassisted cough after intervention. RESULTS: Twenty-eight children (24 boys, 4 girls; mean ± SD age, 12 ± 3 y) completed the study. No clinically or statistically significant changes were found in the cough peak flow after the application of a manually assisted cough by parents or caregivers (95% CI -11 to 11 L/min) or by physiotherapists (95% CI -6 to 14 L/min). CONCLUSIONS: Parents and caregivers and health-care providers were ineffective at increasing cough peak flow in children with neuromuscular weakness when applying a manually assisted cough. A single training session was insufficient for a parent or caregiver to be able to apply a manually assisted cough effectively on his or her child with neuromuscular weakness. Further research is warranted to guide recommendations on how best to equip parents and caregivers with the skills to help manage children with neuromuscular disease.

Association of rhinovirus with exacerbations in young children affected by cystic fibrosis: Preliminary data.

Rhinovirus (RV) is a common respiratory viral infection linked to worsening of chronic respiratory diseases including cystic fibrosis (CF) and asthma. RV was tested by RT-PCR in samples (n = 465) collected from the upper (nasal swab, oropharyngeal suction, and sputum) and lower (bronchoalveolar washings) respiratory tract of 110 children with CF. Air samples (n = 52) collected from the operating theatres and outpatient clinics were tested for RV. RV was found in 43% of children <5 years suffering an exacerbation, and 12% of older children (5-17 years). RV particles were detected in the air of clinic rooms. Detection of RV is important in better understanding viral infections in patients with CF.

Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline.

Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non-invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence-based physiotherapy care to people with CF in Australia and New Zealand.

Diagnostic accuracy and distress associated with oropharyngeal suction in cystic fibrosis.

BACKGROUND: Early detection of bacterial pathogens in the lower airway is an important part of managing CF. This study aimed to assess the diagnostic accuracy of oropharyngeal suction (OPS) samples in obtaining airway bacterial cultures in young children with cystic fibrosis (CF), and the level of child distress caused by obtaining OPS samples. METHODS: Young children with CF undergoing broncho-alveolar lavage (BAL) as part of concurrent research or routine annual surveillance were studied. OPS was performed by stimulating a cough and suctioning the back of the oropharynx in the awake child to replicate clinical practice. BAL of the right upper, middle and lingula lobes was then performed. Samples were sent for standard bacterial culture. The child's distress during OPS was rated using the Groningen Distress Scale (1=calm, 2=timid/nervous, 3=serious distress but still under control, 4=serious distress with loss of control, 5=panic). RESULTS: There were 65 paired samples obtained from 39 children (21 boys, mean age on day of first sampling was 34.1months, SD 19.1months). For Pseudomonas aeruginosa, specificity, sensitivity, NPV and PPV with 95% CI were 98% (87-99), 75% (20-96), 98% (91-98) and 60% (15-93%) respectively. In all age groups combined, median level of distress was 3 (IQR 2-4), with distress highest in 2 and 3year olds, with a median of 4 (IQR 3-4). CONCLUSION: OPS has diagnostic utility in determining the absence of organisms in the lower airway, with specificity for P.aeruginosa detection of 98%. However, a positive OPS result is not necessarily a good indicator of lower airway infection. Distress levels were high during OPS, mostly in 2 and 3year olds.

Use of the Lung Flute for sputum induction in children with cystic fibrosis: a pilot study.

UNLABELLED: This study aimed to assess the effectiveness of the Lung Flute in obtaining a sputum sample from children with cystic fibrosis (CF) that were not productive of sputum with coughing alone. Children attending an outpatient CF clinic who were not able to provide a sample with coughing alone were eligible. Each child used the Lung Flute on two occasions at least one month apart. The primary outcome was expectoration of a sputum sample. Secondary outcomes were sputum microbiology, time taken for the procedure, and ease of use of the device as assessed by the patient using a visual analogue scale (VAS), with 0/10 representing very easy and 10/10 representing very hard. Twenty-five children participated (15 males, mean age 12.7 range 6.5-17.9). Overall, a sputum sample was obtained on 26/50 (52%) uses of the device. In children that presented with a moist cough, a sample was obtained on 17/17 (100%) occasions, compared to 9/33 (27%) occasions when a child presented with a dry cough. A positive culture result for at least one known CF pathogen was found in 24/26 samples. Culture results from obtained samples resulted in management changes in 12 cases. Mean time taken to obtain a sample was 9.8 min (SD 2.2). Mean ease of use on the VAS was 1.5 (SD 1.6). CONCLUSION: The lung flute appears to be a clinically useful and easy device for sputum induction in children with CF. Further research comparing its effectiveness to other sputum induction methods is warranted.

Annual Review Clinic improves care in children with cystic fibrosis.

BACKGROUND: It is unclear whether annual multidisciplinary reviews in cystic fibrosis (CF) patients should be conducted in dedicated annual review (AR) clinics or during continuous assessments throughout the year. Our aim was to assess the effect of introducing an AR clinic. METHODS: A retrospective written and electronic record review of CF patients was carried out for 2007 (no AR Clinic) and 2010 (established AR Clinic) calendar years. An internet-based satisfaction survey was distributed to families attending the AR clinic. RESULTS: In total, 123 children (mean age 9.5 years, range 1.32-18.8 years) and 141 children (8.3 years, 1.1-18.3 years) were included in 2007 and 2010 respectively. There was a significant increase in multidisciplinary reviews (documented annual review 28% vs 85%, P < 0.001; dietary assessment 46% vs 92%, P < 0.001) and investigations (OGTT 2% vs 74%, P < 0.001; abdominal ultrasound 35% vs 85%, P < 0.001) conducted after the introduction of AR clinic. The majority of the families surveyed (85%) were satisfied or very satisfied with the AR clinic. CONCLUSIONS: CF AR clinic significantly improves the number of annual investigations and multidisciplinary reviews performed. Families were satisfied with this new process.

Acid and non-acid reflux during physiotherapy in young children with cystic fibrosis.

BACKGROUND: Gastro-esophageal reflux (GOR) may contribute to lung disease in children with cystic fibrosis (CF). There is conflicting evidence regarding the effect of chest physiotherapy (CPT) in the head-down position on GOR. Furthermore, there is currently no evidence on the impact of physiotherapy on GOR as assessed by pH-multichannel intraluminal impedance (pH-MII). AIMS: (1) To characterize GOR in young children with CF. (2) To determine whether the head-down position during physiotherapy exacerbates GOR. METHODS: Children were studied using pH-MII monitoring over 24-hr, during which they received two 20-min sessions of CPT. One session was performed in "modified" drainage positions with no head-down tilt and the alternate session in "gravity-assisted" drainage positions, which included 20° head-down tilt. RESULTS: Twenty children with CF (8 males), median age 12 months (range 8-34) were recruited. A total of 1,374 reflux episodes were detected in all children, of which 869 (63%) were acid and 505 (37%) were non-acid. Seventy-two percent of the episodes migrated proximally. During CPT, there was no significant difference between total number of reflux episodes in the modified or gravity-assisted positions, median [inter-quartile range (IQR)] 1 (0-2.5) compared to 1 (0.75-3) episode, respectively, P = 0.63. There was also no significant difference between the number of reflux episodes which migrated proximally, median (IQR) 1 (0-2) compared to 0 (0-2) episodes, respectively, P = 0.75. CONCLUSION: In young children with CF, GOR is primarily acidic and proximal migration is common. Physiotherapy in the head-down position does not appear to exacerbate GOR. The impact of GOR on lung disease remains to be elucidated.