Consensus-Based Best Practice Guidelines for the Management of Spinal Deformity and Associated Tumors in Pediatric Neurofibromatosis Type 1: Screening and Surveillance, Surgical Intervention, and Medical Therapy.

BACKGROUND: Spinal conditions, such as scoliosis and spinal tumors, are prevalent in neurofibromatosis type 1 (NF1). Despite the recognized importance of their early detection and treatment, there remain knowledge gaps in how to approach these manifestations. The purpose of this study was to utilize the experience of a multidisciplinary committee of experts to establish consensus-based best practice guidelines (BPGs) for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric patients with NF1. METHODS: Using the results of a prior systematic review, 10 key questions that required further assessment were first identified. A committee of 20 experts across medical specialties was then chosen based on their clinical experience with spinal deformity and tumors in NF1. These were 9 orthopaedic surgeons, 4 neuro-oncologists/oncologists, 3 neurosurgeons, 2 neurologists, 1 pulmonologist, and 1 clinical geneticist. An initial online survey on current practices and opinions was conducted, followed by 2 additional surveys via a formal consensus-based modified Delphi method. The final survey involved voting on agreement or disagreement with 35 recommendations. Items reaching consensus (≥70% agreement or disagreement) were included in the final BPGs. RESULTS: Consensus was reached for 30 total recommendations on the management of spinal deformity and tumors in NF1. These were 11 recommendations on screening and surveillance, 16 on surgical intervention, and 3 on medical therapy. Five recommendations did not achieve consensus and were excluded from the BPGs. CONCLUSION: We present a set of consensus-based BPGs comprised of 30 recommendations for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric NF1.

Does pulmonary function improve after surgical correction of adult idiopathic scoliosis?

PURPOSE: The aim was to investigate pulmonary function after surgical correction of adult idiopathic scoliosis. METHODS: This study included 146 adult scoliosis patients aged 20-50 years (main curve in thoracic spine). Respiratory function was assessed as predicted forced vital capacity (%FVC) and the ratio of forced expiratory volume in 1 s / FVC (%FEV1) preoperatively and 2 years postoperatively and classified as a normal function (≥ 80%), mild impairment (≥ 65% and < 80%), and moderate impairment (< 65%). RESULTS: Preoperative %FVC and %FEV1 were 85.3% and 85.4%, which were 81.5% and 87.5% at 2 years post-surgery. The preoperative %FVC was mild and moderate in 39 (26.7%) and 12 patients (11.6%), respectively. The %FVC significantly improved (+ 6.2% ± 11.4%, P < 0.001) postoperatively for moderate severity but significantly decreased postoperatively (- 6.4% ± 9.4%, P < 0.001) for normal function. The preoperative %FEV1 was mild and moderate in 27 (18.5%) and 0 patients, respectively. The %FEV1 significantly improved postoperatively (6.3% ± 5.3%, P < 0.001) for mild severity but did not significantly change for normal severity. Twenty-three (15.8%) and 41 (28.1%) patients showed improved ⊿%FVC and ⊿% FEV1 > 5%. Logistic regression analysis showed that preoperative %FVC and %FEV1 severities were independent factors affecting postoperative recovery of %FVC (OR 0.95) and %FEV1 (OR 0.85). CONCLUSION: Pulmonary function improved in patients with preoperative pulmonary impairment of < 65% in %FVC and < 80% in %FEV1, and the real improvement was limited to patients with severe preoperative impairment.

Low Preoperative Lung Functions in Children With Early Onset Scoliosis Predict Postoperative Length of Stay.

INTRODUCTION: Children with early onset scoliosis (EOS) undergoing spine surgery often have significant respiratory disease. Preoperative risk assessments that predict an increased length of hospital stay (LOS) for this group have not been previously evaluated. METHODS: A voluntary protocol using preoperative lung function studies began among participants of a multicenter registry in 2016. Preoperative assessments were standardized to include spirometry, blood hemoglobin levels, serum bicarbonate, albumin and prealbumin; radiographic parameters of the spine, C-EOS classification and need for preoperative pulmonary assistance before initial growth friendly device insertion or "definitive" spine fusion. Primary outcome was LOS postoperatively. Data, including age, diagnosis, and type of surgery, was collected prospectively. Secondary outcomes measured included intensive care unit LOS, requirement for new pulmonary assistance on discharge, and pulmonary complications. Groups were compared using the Fisher exact tests. RESULTS: Of 525 children enrolled, 101 (20%) had preoperative spirometry. Median age was 8.9 years [interquartile range (IQR): 4.27]. Etiologies for EOS included 29 neuromuscular (28%), 33 idiopathic (32%), 19 syndromic (19%), and 22 congenital (21%) scoliosis. Eighty (78%) had growing rod (GR) insertions; 23 (22%) had spine fusion SF. Eighteen subjects (17%) were hospitalized ≥7 days (median=9 d); 83 had a LOS <7 days (median=3 d). Percentage of forced vital capacity (FVC%) predicted was inversely associated with LOS ≥7 days with a median of 75.3% (IQR: 41.7) for LOS <7 days and 51.7% (IQR: 41.6) (P=0.02). There were no detectable differences in LOS for other preoperative values. CONCLUSION: FVC predicted ≤50% preoperatively in children undergoing initial growth friendly rod insertion or definitive fusion after growth friendly treatment is associated with an increased risk of postoperative hospital stays ≥7 days. As demonstrated in previous studies, severe restrictive lung disease (FVC% predicted at or below 50%) is associated with increased risk of poorer outcomes for EOS patients.

Preoperative 6-Minute Walk Performance in Children With Congenital Scoliosis.

BACKGROUND: The 6-minute walk test (6MWT) is used to assess the function of cardiopulmonary and neuromuscular conditions in adults and children. The primary research question was to determine the relationship between 6MWT distance and forced vital capacity (FVC) and the major curve among children with congenital scoliosis with rib anomalies. METHODS: The authors recorded 6MWT distance in meters, FVC as a percentage of predicted normal value using arm span for height (FVC%), and Cobb angle in 20 children (13 girls; average age, 6.7±1.3 y) with congenital scoliosis before outpatient surgical treatment. The 6MWT uses a standardized protocol and measures distance traveled in 6 minutes on a flat surface. The authors then determined the correlation between these measures using linear regression analysis. RESULTS: The Cobb angle of the major curvature was 55.4±20.5 degrees. The type of vertebral anomaly was mixed in 17 cases, formation failure in 2 cases, and segmentation failure in 1 case. The range of rib anomalies was 3.4±3.9 levels; 15 and 5 patients, respectively, had unilateral and bilateral rib anomalies. FVC and FVC% were 0.7±0.2 L and 60%±19%, respectively. The ratio of forced expiratory volume at 1 second to FVC (FEV1/FVC), which indicates obstructive lung disease, was normal at 93%±7%. The 6MWT distance was 386.3±59.4 m, which was ≤10% of the predicted distance for normal children. No child was able to walk the normal distance on the basis of published norms. 6MWT distance was significantly correlated with arm span (ρ=0.46, P=0.04) and major curve (ρ=-0.61, P=0.004), but not with FVC% (ρ=0.17, P=0.49). CONCLUSIONS: The 6MWT distance is a feasible measure of function and is substantially reduced before surgery in children with thoracic congenital scoliosis with rib anomalies. The 6MWT distance was significantly correlated with a major curve but not with FVC%. 6MWT distance is not affected by moderate lung function impairment. LEVEL OF EVIDENCE: Level IV-retrospective cohort study.

Clinical Issues for Pediatric Pulmonologists Managing Children With Thoracic Insufficiency Syndrome.

Thoracic insufficiency Syndrome (TIS) is a recently coined phrase to describe children with spine and chest wall deformities, inherited and acquired, who have respiratory impairment, and are skeletally immature. This population has both restrictive and less often obstructive lung disease due to changes in spine and rib configuration which reduce lung volume, stiffen the chest wall, and reduce respiratory muscle strength. Although the population is heterogeneous with regard to age of onset, etiology, severity of deformity, and rate of progression of the deformity, there are common issues that arise which can be addressed by pediatric pulmonologists. These are illustrated in this review by using Early Onset Scoliosis as a common form of TIS. The pulmonary issues pertaining to TIS require collaboration with multi-disciplinary teams, particularly spine surgeons, in order to make decisions about non-surgical and surgical strategies, timing of surgery and medical supportive care over time. Pulmonary input about respiratory function should be used in conjunction with structural features of each deformity in order to determine the impact of the deformity and the response to various treatment options. In those patients with residual lung function impairment as young adults, pediatric pulmonologists must also ensure successful transition to adult care.

A decade on: Follow-up findings of indigenous children with bronchiectasis.

OBJECTIVE: The sole prospective longitudinal study of children with either chronic suppurative lung disease (CSLD) or bronchiectasis published in the current era was limited to a single center. We sought to extend this study by evaluating the longer-term clinical and lung function outcomes and their associated risk factors in Indigenous children of adolescents from Australia, Alaska, and New Zealand who participated in our previous CSLD or bronchiectasis studies during 2004-2010. METHODS: Between 2015 and 2018, we evaluated 131 out of 180 (72.8%) children of adolescents from the original studies at a single follow-up visit. We administered standardized questionnaires, reviewed medical records, undertook clinical examinations, performed spirometry, and scored available chest computed tomography scans. RESULTS: Participants were seen at a mean age of 12.3 years (standard deviation: 2.6) and a median of 9.0 years (range: 5.0-13.0) after their original recruitment. With increasing age, rates of acute lower respiratory infections (ALRI) declined, while lung function was mostly within population norms (median forced expiry volume in one-second = 90% predicted, interquartile range [IQR]: 81-105; forced vital capacity [FVC] = 98% predicted, IQR: 85-114). However, 43 out of 111 (38.7%) reported chronic cough episodes. Their overall global rating judged by symptoms, including ALRI frequency, examination findings, and spirometry was well (20.3%), stable (43.9%), or improved (35.8%). Multivariable regression identified household tobacco exposure and age at first ALRI-episode as independent risk factors associated with lower FVC% predicted values. CONCLUSION: Under our clinical care, the respiratory outcomes in late childhood or early adolescence are encouraging for these patient populations at high-risk of premature mortality. Prospective studies to further inform management throughout the life course into adulthood are now needed.

The Spinal Structure and Lung Function Relationship in an Untreated Nonambulatory Myelomeningocele Group of Patients.

INTRODUCTION: The relationship between spinal structure and respiratory function has been coined as thoracic insufficiency syndrome and is defined as the inability of the thorax to support normal respiratory function or lung growth. Little is known about what supports this relationship in untreated nonambulatory myelomeningocele patients. METHODS: A prospective cross-sectional study of nonambulatory myelodysplasia patients was performed. Anatomic, radiographic, and functional parameters were evaluated to validate the respiratory-spinal structure relationship. Thirty-one patients diagnosed with nonambulatory myelomeningocele fulfilled the inclusion criteria. RESULTS: The imaging study confirmed the spinal deformity. Lung functions measured in this patient population describe reduced lung volumes by CT lung volume reconstruction, reduced vital capacity by spirometry, and reduced total lung capacity by the nitrogen washout method. Together, these findings suggest moderate restrictive respiratory disease. The blood count study did not show evidence of anemia or other blood disturbances. Echocardiogram analysis did not show pulmonary hypertension in any patient. CONCLUSION: The data validate the relationship between spinal structure and lung function. However, there is no simple structural feature that could help to diagnose thoracic insufficiency syndrome. Thus, the diagnosis continues to be based on a combination of clinical findings and radiological and respiratory function evaluations. LEVEL OF EVIDENCE: Level III.

Early-Onset Spinal Deformity in Skeletal Dysplasias: A Multicenter Study of Growth-Friendly Systems.

PURPOSE: Severe, early-onset spinal deformity is common in patients with skeletal dysplasia. These deformities often present at young ages and are associated with significant pulmonary dysfunction. The objective of this study is to verify the effectiveness of growth-friendly spinal instrumentation systems in promoting growth in patients with skeletal dysplasia and early-onset kyphoscoliosis. METHODS: A retrospective, multicenter comparative cohort study was performed. Twenty-three patients identified to have a skeletal dysplasia (SKD) were evaluated for diagnosis, age at treatment, gender, and type of growing rod construct (spine vs. rib constructs). Patients were matched by age and construct type with similarly treated patients with early-onset scoliosis (CON) without skeletal dysplasia. Radiographic parameters including maximum coronal and sagittal Cobb angle with levels, T1-S1 height, and T1-T12 height were measured. RESULTS: T1-T12 (12.8 vs. 15.2 cm, p = .01) and T1-S1 (21.2 vs. 24.5 cm, p = .05) heights were significantly shorter for the SKD group at implantation, and kyphosis tended to be more severe in children with SKD (p = .80 and .07, respectively). Kyphosis did not improve with treatment. Scoliosis improved (p < .01), and ΔT1-T12 and ΔT1-S1 significantly increased in both groups (p < .01). Complication rates were similar between the two groups; however, patients with SKD had more intraoperative monitoring changes and hardware failures (p < .005). CONCLUSION: Although patients with SKD start with shorter spine lengths, gains in spine length appear to be comparable to other forms of EOS. Neuromonitoring changes and implant failures are more common in the SKD group. SIGNIFICANCE: The effectiveness of growth-friendly techniques in promoting growth in early-onset spinal deformities in patients with skeletal dysplasia has not been previously studied. We report the first comprehensive review of this topic. Growth-friendly techniques are an appropriate treatment option in this patient population.

Best practices in peri-operative management of patients with skeletal dysplasias.

Patients with skeletal dysplasia frequently require surgery. This patient population has an increased risk for peri-operative complications related to the anatomy of their upper airway, abnormalities of tracheal-bronchial morphology and function; deformity of their chest wall; abnormal mobility of their upper cervical spine; and associated issues with general health and body habitus. Utilizing evidence analysis and expert opinion, this study aims to describe best practices regarding the peri-operative management of patients with skeletal dysplasia. A panel of 13 multidisciplinary international experts participated in a Delphi process that included a thorough literature review; a list of 22 possible care recommendations; two rounds of anonymous voting; and a face to face meeting. Those recommendations with more than 80% agreement were considered as consensual. Consensus was reached to support 19 recommendations for best pre-operative management of patients with skeletal dysplasia. These recommendations include pre-operative pulmonary, polysomnography; cardiac, and neurological evaluations; imaging of the cervical spine; and anesthetic management of patients with a difficult airway for intubation and extubation. The goals of this consensus based best practice guideline are to provide a minimum of standardized care, reduce perioperative complications, and improve clinical outcomes for patients with skeletal dysplasia.

Early-Onset Scoliosis: A Review of History, Current Treatment, and Future Directions.

Early-onset scoliosis (EOS) is defined as curvature of the spine in children >10° with onset before age 10 years. Young children with EOS are at risk for impaired pulmonary function because of the high risk of progressive spinal deformity and thoracic constraints during a critical time of lung development. The treatment of EOS is very challenging because the population is inhomogeneous, often medically complex, and often needs multiple surgeries. In the past, early spinal fusion was performed in children with severe progressive EOS, which corrected scoliosis but limited spine and thoracic growth and resulted in poor pulmonary outcomes. The current goal in treatment of EOS is to maximize growth of the spine and thorax by controlling the spinal deformity, with the aim of promoting normal lung development and pulmonary function. Bracing and casting may improve on the natural history of progression of spinal deformity and are often used to delay surgical intervention or in some cases obviate surgery. Recent advances in surgical implants and techniques have led to the development of growth-friendly implants, which have replaced early spine fusion as the surgical treatment of choice. Treatment with growth-friendly implants usually requires multiple surgeries and is associated with frequent complications. However, growth-friendly spine surgery has been shown to correct spinal deformity while allowing growth of the spine and subsequently lung growth.

Respiratory exacerbations in indigenous children from two countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis.

BACKGROUND: Acute respiratory exacerbations (AREs) cause morbidity and lung function decline in children with chronic suppurative lung disease (CSLD) and bronchiectasis. In a prospective longitudinal cohort study, we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis. METHODS: Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia (n = 57) and Alaska (n = 36) during 2004 to 2009 were followed for > 3 years. Standardized parent interviews, physical examinations, and medical record reviews were undertaken at enrollment and every 3 to 6 months thereafter. RESULTS: Ninety-three children experienced 280 AREs (median = 2, range = 0-11 per child) during the 3-year period; 91 (32%) were associated with pneumonia, and 43 (15%) resulted in hospitalization. Of the 93 children, 69 (74%) experienced more than two AREs over the 3-year period, and 28 (30%) had more than one ARE in each study year. The frequency of AREs declined significantly over each year of follow-up. Factors associated with recurrent (two or more) AREs included age < 3 years, ARE-related hospitalization in the first year of life, and pneumonia or hospitalization for ARE in the year preceding enrollment. Factors associated with hospitalizations for AREs in the first year of study included age < 3 years, female caregiver education, and regular use of bronchodilators. CONCLUSIONS: AREs are common in children with CSLD/bronchiectasis, but with clinical care and time AREs occur less frequently. All children with CSLD/bronchiectasis require comprehensive care; however, treatment strategies may differ for these patients based on their changing risks for AREs during each year of care.

Three clinically distinct chronic pediatric airway infections share a common core microbiota.

RATIONALE: DNA-based microbiological studies are moving beyond studying healthy human microbiota to investigate diverse infectious diseases, including chronic respiratory infections, such as those in the airways of people with cystic fibrosis (CF) and non-CF bronchiectasis. The species identified in the respiratory secretion microbiota from such patients can be classified into those that are common and abundant among similar subjects (core) versus those that are infrequent and rare (satellite). This categorization provides a vital foundation for investigating disease pathogenesis and improving therapy. However, whether the core microbiota of people with different respiratory diseases, which are traditionally associated with specific culturable pathogens, are unique or shared with other chronic infections of the lower airways is not well studied. Little is also known about how these chronic infection microbiota change from childhood to adulthood. OBJECTIVES: We sought to compare the core microbiota in respiratory specimens from children and adults with different chronic lung infections. METHODS: We used bacterial 16S rRNA gene pyrosequencing, phylogenetic analysis, and ecological statistical tools to compare the core microbiota in respiratory samples from three cohorts of symptomatic children with clinically distinct airway diseases (protracted bacterial bronchitis, bronchiectasis, CF), and from four healthy children. We then compared the core pediatric respiratory microbiota with those in samples from adults with bronchiectasis and CF. MEASUREMENTS AND MAIN RESULTS: All three pediatric disease cohorts shared strikingly similar core respiratory microbiota that differed from adult CF and bronchiectasis microbiota. The most common species in pediatric disease cohort samples were also detected in those from healthy children. The adult CF and bronchiectasis microbiota also differed from each other, suggesting common early infection airway microbiota that diverge by adulthood. The shared core pediatric microbiota included both traditional pathogens and many species not routinely identified by standard culture. CONCLUSIONS: Our results indicate that these clinically distinct chronic airway infections share common early core microbiota, which are likely shaped by natural aspiration and impaired clearance of the same airway microbes, but that disease-specific characteristics select for divergent microbiota by adulthood. Longitudinal and interventional studies will be required to define the relationships between microbiota, treatments, and disease progression.

An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy.

BACKGROUND: There is growing recognition and understanding of the entities that cause interstitial lung disease (ILD) in infants. These entities are distinct from those that cause ILD in older children and adults. METHODS: A multidisciplinary panel was convened to develop evidence-based guidelines on the classification, diagnosis, and management of ILD in children, focusing on neonates and infants under 2 years of age. Recommendations were formulated using a systematic approach. Outcomes considered important included the accuracy of the diagnostic evaluation, complications of delayed or incorrect diagnosis, psychosocial complications affecting the patient's or family's quality of life, and death. RESULTS: No controlled clinical trials were identified. Therefore, observational evidence and clinical experience informed judgments. These guidelines: (1) describe the clinical characteristics of neonates and infants (<2 yr of age) with diffuse lung disease (DLD); (2) list the common causes of DLD that should be eliminated during the evaluation of neonates and infants with DLD; (3) recommend methods for further clinical investigation of the remaining infants, who are regarded as having "childhood ILD syndrome"; (4) describe a new pathologic classification scheme of DLD in infants; (5) outline supportive and continuing care; and (6) suggest areas for future research. CONCLUSIONS: After common causes of DLD are excluded, neonates and infants with childhood ILD syndrome should be evaluated by a knowledgeable subspecialist. The evaluation may include echocardiography, controlled ventilation high-resolution computed tomography, infant pulmonary function testing, bronchoscopy with bronchoalveolar lavage, genetic testing, and/or lung biopsy. Preventive care, family education, and support are essential.

Lung function and biomarkers of airway inflammation during and after hospitalization for acute exacerbations of childhood asthma associated with viral respiratory symptoms.

BACKGROUND: There are limited data assessing relationships between biomarkers of inflammation and lung function after hospitalization for asthma exacerbations in children. OBJECTIVE: To assess the associations in asthmatic children among changes in lung function, fraction of exhaled nitric oxide (FENO), and cysteinyl leukotrienes (CysLTs) in exhaled breath condensate (EBC) after hospitalization for acute asthma. METHODS: Spirometry and FENO were measured and EBC collected for CysLT measurement from 40 children during and 1, 2, and 4 weeks after hospitalization for an asthma exacerbation and during a single-study visit for 40 healthy children. RESULTS: Enrollment FENO and EBC CysLT concentrations were higher in the children with asthma than in healthy individuals (mean FENO, 31.6 vs 7 ppb; P < .0001; mean EBC CysLT, 7.9 vs 4.9 ppb; P = .03). Among children with asthma, improvement in lung function reached a plateau within 2 weeks after hospital discharge. The EBC CysLT concentrations were not associated with changes in lung function, use of albuterol, or use of inhaled corticosteroids (ICSs). Among asthmatic children enrollment FENO was not associated with changes in lung function during follow-up. However, among children who had an elevated enrollment FENO (≥25 ppb), patients who did not use ICSs after hospital discharge had lower end-of-study lung function than those who used ICSs. At 2 and 4 weeks after hospital discharge, FENO was higher among patients who reported albuterol use more than twice weekly and among patients who reported no ICS use. CONCLUSION: FENO measured at hospital discharge among children hospitalized with acute asthma may be useful in identifying patients who will respond to ICS therapy.

Update on treatment of childhood bronchiectasis unrelated to cystic-fibrosis.

There are multiple aetiologies for childhood bronchiectasis unrelated to cystic fibrosis. Some of these aetiologies, such as those predisposing to recurrent lung infections, e.g. immunodeficiencies, require treatment of the underlying condition and disease-specific pulmonary pathogens within the airway. Regardless of aetiology, the treatments for bronchiectasis include antibiotics, airway clearance regimens, immunizations to prevent infections, and in some cases asthma therapies. The grade of evidence for specific treatments is low with few randomized controlled trials in children. Extrapolations of care provided to adults with bronchiectasis and patients with cystic fibrosis may not always be justified. Comprehensive care programs for children with bronchiectasis have demonstrated clinically relevant improvements over 2-7 year periods. Multi-center research is needed to rigorously evaluate current treatment practices for children with this disorder.

Structure-respiration function relationships before and after surgical treatment of early-onset scoliosis.

BACKGROUND: Spine and chest wall deformities in children with early onset scoliosis (EOS) frequently impair respiratory function and postnatal growth of the lung. While a relationship between deformity and such impairment has been reported in children with adolescent idiopathic scoliosis it is not well understood in children with early-onset scoliosis (EOS). QUESTIONS/PURPOSES: We therefore describe (1) the preoperative relation between Cobb angle and forced vital capacity (FVC) in infants with EOS; (2) how changes in Cobb angle before and after surgery relate to changes in lung ventilation and perfusion in the right and left lungs. METHODS: We measured FVC in 10 children with EOS < 3 years old using the raised volume rapid thoracic compression (RVRTC) technique and correlated them with Cobb angles. We then measured right lung contributions to total lung ventilation and perfusion using lung scans before and 4 to 57 months after placement of vertical expandable prosthetic titanium ribs (VEPTRs) in 15 children with EOS and correlated changes in right lung function with postoperative changes in Cobb angles. RESULTS: In children 4 to 57 months of age, preoperative FVC (mean value, 83%; range, 63%-109% of predicted values) did not correlate with Cobb angles (mean value, 56º; range, 14°-120º). In children 1.8 to 11.5 years old, right lung ventilation and perfusion were abnormal in eight and seven children, respectively, but neither ventilation nor perfusion predictably normalized despite reductions in Cobb angle postoperatively. CONCLUSIONS: The data extend the age range of children with EOS whose Cobb angles correlate poorly with FVC preoperatively. The data are also consistent with reports that reduced Cobb angles after VEPTR insertion do not correlate with postoperative changes in respiratory function.

Pulmonary exacerbations are associated with subsequent FEV1 decline in both adults and children with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) frequently experience pulmonary exacerbations that may lead to a faster subsequent decline in pulmonary function; however, this relationship has not been clearly established. The purpose of this study was to determine the association between the frequency of pulmonary exacerbations and subsequent forced expiratory volume in 1 sec (FEV(1) ) decline in adults and children with CF. METHODS: Cohort study of subjects followed in the Cystic Fibrosis Foundation Patient Registry from 2003 through 2006. Mixed effects modeling was used to estimate differences in rates of decline in FEV(1) in 2004-2006 for patients with 0, 1, 2, or 3+ pulmonary exacerbation(s) in 2003. RESULTS: Of 8,490 subjects who met inclusion criteria, 60% had 0 exacerbations, 23% had 1, 10% had 2, and 7% had 3+ exacerbations in 2003. Compared to children with no pulmonary exacerbations in 2003, children with one or more exacerbations experienced a significantly (P < 0.001) greater rate of FEV(1) decline in 2004-2006. In contrast, among adults, only those with 3+ exacerbations in 2003 had a significantly (P = 0.01) greater rate of FEV(1) decline in 2004-2006 than those with no exacerbations in 2003. CONCLUSIONS: There is a strong association between the frequency of pulmonary exacerbations and subsequent decline in pulmonary function. In adults, having 3+ exacerbations, and among children, having any exacerbations is associated with a greater rate of decline in the ensuing 3 years. Improved prevention, identification, and treatment of pulmonary exacerbations are likely to have long-term benefits for patients with CF, especially children.

Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation.

RATIONALE: Patients with cystic fibrosis periodically experience pulmonary exacerbations. Previous studies have noted that some patients' lung function (FEV(1)) does not improve with treatment. OBJECTIVES: To determine the proportion of patients treated for a pulmonary exacerbation that does not recover to spirometric baseline, and to identify factors associated with the failure to recover to spirometric baseline. METHODS: Cohort study using the Cystic Fibrosis Foundation Patient Registry from 2003-2006. We randomly selected one pulmonary exacerbation treated with intravenous antibiotics per patient and compared the best FEV(1) in the 3 months after treatment with the best FEV(1) in the 6 months before treatment. Recovery to baseline was defined as any FEV(1) in the 3 months after treatment that was greater than or equal to 90% of the baseline FEV(1). Multivariable logistic regression was used to estimate associations with the failure to recover to baseline FEV(1). MEASUREMENTS AND MAIN RESULTS: Of 8,479 pulmonary exacerbations, 25% failed to recover to baseline FEV(1). A higher risk of failing to recover to baseline was associated with female sex; pancreatic insufficiency; being undernourished; Medicaid insurance; persistent infection with Pseudomonas aeruginosa, Burkholderia cepacia complex, or methicillin-resistant Staphylococcus aureus; allergic bronchopulmonary aspergillosis; a longer time since baseline spirometric assessment; and a larger drop in FEV(1) from baseline to treatment initiation. CONCLUSIONS: For a randomly selected pulmonary exacerbation, 25% of patients' pulmonary function did not recover to baseline after treatment with intravenous antibiotics. We identified factors associated with the failure to recover to baseline, allowing clinicians to identify patients who may benefit from closer monitoring and more aggressive treatment.

Return of FEV1 after pulmonary exacerbation in children with cystic fibrosis.

RATIONALE: Lung function (FEV(1)) generally improves during treatment of pulmonary exacerbations in patients with cystic fibrosis (CF). However, it is unclear how often return to previous baseline FEV(1) is achieved. OBJECTIVES: (1) To determine the proportion of pediatric patients with CF treated for a pulmonary exacerbation who fail to recover to baseline FEV(1) and (2) to identify factors associated with this failure. METHODS: We performed a case-control analysis of patients from a single pediatric CF center admitted for their first pulmonary exacerbation in 2001-2006. Patients were considered to have recovered to baseline FEV(1) if their best FEV(1) within the 3 months following treatment was >or=95% of the best FEV(1) during the 6 months prior to treatment. Logistic regression was used to estimate associations between clinical characteristics and failure to regain baseline FEV(1). RESULTS: Of 104 patients, 24 (23.1%) did not recover to baseline FEV(1). The adjusted odds ratio of failure to recover to baseline FEV(1) was 1.49 (95% confidence interval [CI] 1.20, 1.86) for every 5% greater decline in FEV(1) from baseline to admission. In exploratory analyses, the adjusted odds ratios for the failure to recover to baseline were also significantly higher for patients who were evaluated in our CF clinic more frequently between the baseline measurement and admission, were younger, or were insured by Medicaid. CONCLUSIONS: Approximately one in four patients with CF failed to recover to baseline lung function after a pulmonary exacerbation despite treatment with intravenous antibiotics. Failure to recover to baseline was associated with the degree of decline in FEV(1) that had occurred prior to hospital admission, suggesting opportunities for earlier intervention to improve lung function outcomes. Additional studies are needed to determine how the failure to recover to baseline affects subsequent FEV(1) decline.