Pulmonology Research

AsthmaNet is a nationwide clinical research network created by the National Heart Lung and Blood Institute in 2009. The purpose of AsthmaNet is to develop and conduct multiple clinical trials that explore new approaches in treating asthma from childhood through adulthood. Children’s serves as one of 13 locations where clinical trials for AsthmaNet are conducted.

The Emory and Children’s cystic fibrosis program serves more pediatric and adult cystic fibrosis (CF) patients than almost any other CF care center in the country. Children’s and Emory have established the Center for CF and Airways Disease Research (CF-AIR): a collaborative research team centered around translational and basic research in CF that takes advantage of the availability of CF patients at our Cystic Fibrosis Care Center and other assets at Children’s, Emory, Georgia Tech and elsewhere in Atlanta. This is achieved by supporting research projects and research cores that will draw together investigators with various expertise to solve critical problems associated with CF disease.

CF-AIR has worked with several other pediatric hospital and research institutions across the nation, to collaborate on studies such as this publication in the Journal of Cystic Fibrosis.

The Severe Asthma Research Program (SARP) is the world’s most comprehensive study of adults and children with severe asthma, linking seven asthma clinical university centers through a network sponsored by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH). The Emory Children’s Center serves as one of the sites for pediatric participants. To date, over 1,500 asthma patients have participated. The network’s mission is to improve the understanding of severe asthma to develop better treatments.

Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test

Kasi AS, Wee CP, Keens TG, Salinas DB. Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test. Lung. 2021 Feb;199(1):37-41. doi: 10.1007/s00408-020-00412-8. Epub 2021 Jan 3. PMID: 33389068.

Serum Anti-PAD4 Autoantibodies are Present in Cystic Fibrosis Children and Increase with Age and Lung Disease Severity

Linnemann RW, Yadav R, Zhang C, Sarr D, Rada B, Stecenko AA. Serum anti-PAD4 autoantibodies are present in cystic fibrosis children and increase with age and lung disease severity. Autoimmunity. 2022 Mar;55(2):109-117. doi: 10.1080/08916934.2021.2021193. Epub 2022 Jan 4. PMID: 35199621; PMCID: PMC9996683.

• The aim of this study was to investigate clinical predictors of serum anti-PAD4 autoantibody (PAD4 Ab) levels in cystic fibrosis subjects with a wide range of ages from early childhood through middle age.

Impact of Viral Respiratory Infections on Pulmonary Exacerbations in Children with Cystic Fibrosis

Gonzalez-Rosales N, Kasi AS, McCracken CE, Silva GL, Starks M, Stecenko A, Guglani L. Impact of viral respiratory infections on pulmonary exacerbations in children with cystic fibrosis. Pediatric Pulmonology. 2023 Mar;58(3):871-877. doi: 10.1002/ppul.26267. Epub 2022 Dec 12. PMID: 36479634.

• A retrospective review of pediatric patients with CF who underwent nasopharyngeal respiratory viral panel testing during hospitalization for a pulmonary exacerbations (PEs) between 2011 and 2018 was conducted. Patients were dichotomized into viral-positive and viral-negative groups. The results of spirometry, respiratory cultures, duration of hospitalization, and risk for subsequent PEs were analyzed.

Impaired Ventilation During 6-min Walk Test in Congenital Central Hypoventilation Syndrome

Ghosh RN, Guglani L, Westbrook AL, Mao CY, Bai S, Keens TG, Kasi AS. Impaired ventilation during 6-min walk test in congenital central hypoventilation syndrome. Pediatric Pulmonology. 2022 Jul;57(7):1660-1667. doi: 10.1002/ppul.25940. Epub 2022 May 5. PMID: 35460211.

• Despite normal oxygenation and ventilation at rest and during sleep on assisted ventilation, patients with CCHS can develop hypoxemia and hypercapnia during submaximal exercise. Our study highlights the importance of assessing ventilatory responses during submaximal exercise in patients with CCHS regardless of their PHOX2B genotype.

Tracheostomy Decannulation to Noninvasive Positive Pressure Ventilation in Congenital Central Hypoventilation Syndrome

Kasi AS, Anand N, Harford KL, Landry AM, Alfonso KP, Taylor M, Keens TG, Leu RM. Tracheostomy decannulation to noninvasive positive pressure ventilation in congenital central hypoventilation syndrome. Sleep Breath. 2022 Mar;26(1):133-139. doi: 10.1007/s11325-021-02368-2. Epub 2021 Apr 14. PMID: 33852109.

• This study aimed to describe the clinical course and outcome of children with congenital central hypoventilation syndrome who underwent tracheostomy decannulation and transitioned from PPV-T to NPPV.

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach

Kasi AS, Li H, Harford KL, Lam HV, Mao C, Landry AM, Mitchell SG, Clifton MS, Leu RM.

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach. Journal of Multidisciplinary Healthcare. 2022 Mar 8;15:455-469. doi: 10.2147/JMDH.S284782. PMID: 35360554; PMCID: PMC8963195.

• Despite an established PHOX2B genotype and phenotype correlation, patients have variable and heterogeneous clinical manifestations requiring the formulation of an individualized plan of care based on collaboration between the pulmonologist, otolaryngologist, cardiologist, anesthesiologist, gastroenterologist, sleep medicine physician, geneticist, surgeon, oncologist and respiratory therapist.

Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations

Kasi AS, Li H, Jurgensen TJ, Guglani L, Keens TG, Perez IA. Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations. J Clin Sleep Med. 2021 Oct 1;17(10):2049-2055. doi: 10.5664/jcsm.9370. PMID: 33983112; PMCID: PMC8494081.

• Congenital central hypoventilation syndrome (CCHS) is a rare disorder affecting the autonomic nervous system that is caused by variants in the paired-like homeobox 2B (PHOX2B) gene. About 10% of patients with CCHS have nonpolyalanine repeat mutations (NPARM) that are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and increased neural crest tumor risk. However, some patients with NPARM have milder phenotypes. Our objective was to describe the phenotypes in patients with CCHS PHOX2B NPARM.

Annual Respiratory Evaluations in Congenital Central Hypoventilation Syndrome and Changes in Ventilatory Management

Shah AS, Leu RM, Keens TG, Kasi AS. Annual Respiratory Evaluations in Congenital Central Hypoventilation Syndrome and Changes in Ventilatory Management. Pediatric Allergy Immunology Pulmonology. 2021 Sep;34(3):97-101. doi: 10.1089/ped.2021.0072. Epub 2021 Aug 27. PMID: 34449269; PMCID: PMC8664117.

• This study aimed to determine if annual in-hospital respiratory evaluations in patients with congenital central hypoventilation syndrome led to changes in ventilatory management.

Recurrent Apnoea and Respiratory Failure in an Infant: Congenital Central Hypoventilation Syndrome with a Novel PHOX2B Gene Variant

Anand N, Leu RM, Simon D, Kasi AS. Recurrent apnoea and respiratory failure in an infant: congenital central hypoventilation syndrome with a novel PHOX2B gene variant. British Medical Journal Case Report. 2021 Mar 19;14(3):e239633. doi: 10.1136/bcr-2020-239633. PMID: 33741569; PMCID: PMC7986671.

Pediatric pulmonology 2021 year in review: Rare and diffuse lung disease

Popler J, Vece TJ, Liptzin DR, Gower WA. Pediatric pulmonology 2021 year in review: Rare and diffuse lung disease. Pediatr Pulmonol. 2023 Feb;58(2):374-381. doi: 10.1002/ppul.26227. Epub 2022 Dec 1. PMID: 36426677.

• This annual review discusses manuscripts published in Pediatric Pulmonology in 2021 in (1) children's interstitial and diffuse lung disease, (2) congenital airway and lung malformations, and (3) noncystic fibrosis bronchiectasis including primary ciliary dyskinesia.

Multidisciplinary feeding treatment for a patient with inaterstitial lung disease

Stubbs KH, McMahon MXH, Popler J, Berry RC, Sharp WG. Multidisciplinary feeding treatment for a patient with interstitial lung disease. Pediatr Pulmonol. 2022 Dec;57(12):3183-3185. doi: 10.1002/ppul.26146. Epub 2022 Sep 26. PMID: 36100872.

• This paper presents an encounter in which we safely and effectively treated ARFID as evidenced by underweight and dependence on a nutritionally complete formula in a 3-year-old male with ILD using a multidisciplinary approach to treatment.

Heterogeneous Pulmonary Phenotypes in Filamin A Mutation-Related Lung Disease

Shah AS, Black ED, Simon DM, Gambello MJ, Garber KB, Iannucci GJ, Riedesel EL, Kasi AS. Heterogeneous Pulmonary Phenotypes in Filamin A Mutation-Related Lung Disease. Pediatr Allergy Immunol Pulmonol. 2021 Mar;34(1):7-14. doi: 10.1089/ped.2020.1280. PMID: 33734874; PMCID: PMC8082031.

• This study retrospectively reviewed pediatric patients with variants in FLNA in a tertiary children's hospital. The clinical features, genotype, management and outcomes were analyzed.

Hypoxaemia and interstitial lung disease in an infant with hypothyroidism and hypotonia

Lynn MM, Simon D, Kasi AS. Hypoxaemia and interstitial lung disease in an infant with hypothyroidism and hypotonia. BMJ Case Rep. 2020 Dec 22;13(12):e238466. doi: 10.1136/bcr-2020-238466. PMID: 33370995; PMCID: PMC7757479.

• Our case highlights the importance of genetic studies to diagnose brain-thyroid-lung syndrome in infants with hypothyroidism, hypotonia and lung disease.

Sleep disturbances in parental caregivers and patients with congenital central hypoventilation syndrome

Finch CE, Leu RM, Harford KL, Westbrook AL, Kasi AS. Sleep disturbances in parental caregivers and patients with congenital central hypoventilation syndrome. J Clin Sleep Med. 2023 Mar 1;19(3):549-554. doi: 10.5664/jcsm.10384. PMID: 36541215; PMCID: PMC9978429.

• Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by impaired control of breathing caused by paired-like homeobox 2B (PHOX2B) gene variants, necessitating lifelong assisted ventilation (AV). This study aimed to assess sleep quality in patients with CCHS and their parents using sleep questionnaires.

Images: Caffeine therapy for central sleep apnea, hypoxemia, and hypoventilation in a term neonate

Shah AS, Leu RM, Shah SP, Martinez F, Kasi AS. Images: Caffeine therapy for central sleep apnea, hypoxemia, and hypoventilation in a term neonate. J Clin Sleep Med. 2023 Feb 7. doi: 10.5664/jcsm.10504. Epub ahead of print. PMID: 36747487.

• The evaluation of higher-risk infants with brief resolved unexplained events (BRUE) and term infants with central sleep apnea (CSA) can be clinically challenging due to the multitude of potential etiologies. This study reports a 7-day-old term neonate hospitalized for evaluation of BRUE with oxygen desaturations during sleep.

A meta-analysis of diagnostic test performance of peripheral arterial tonometry studies

Iftikhar IH, Finch CE, Shah AS, Augunstein CA, Ioachimescu OC. A meta-analysis of diagnostic test performance of peripheral arterial tonometry studies. J Clin Sleep Med. 2022 Apr 1;18(4):1093-1102. doi: 10.5664/jcsm.9808. PMID: 34879903; PMCID: PMC8974372.

• The objective of this meta-analysis was to analyze agreement in apnea-hypopnea index (AHI) determination between peripheral arterial tonometry (PAT) and polysomnography (PSG) studies.

Images: Sleep-disordered breathing and hypoventilation in a child with obesity and hypothalamic dysfunction

Ghosh R, Malik M, Daley TC, Kasi AS. Images: Sleep-disordered breathing and hypoventilation in a child with obesity and hypothalamic dysfunction. J Clin Sleep Med. 2022 Jan 1;18(1):339-342. doi: 10.5664/jcsm.9636. PMID: 34534067; PMCID: PMC8807918.

• Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare and potentially lethal disorder of respiratory control, autonomic and hypothalamic dysfunction of unknown etiology. This study reports a 15-year-old girl with ROHHAD who developed hyperphagia, rapid weight gain and cardiorespiratory arrest.

Do Repeated Spirometry Maneuvers Affect Respiratory Mechanics? Resistance Is Not Futile

Kasi AS, Guglani L. Do Repeated Spirometry Maneuvers Affect Respiratory Mechanics? Resistance Is Not Futile. Indian J Pediatr. 2022 Dec;89(12):1169-1170. doi: 10.1007/s12098-022-04353-3. Epub 2022 Sep 7. PMID: 36068401.

• This study analyzes the impact of repeated forced exhalation spirometry maneuvers on airway resistance. 

Ventilator change in children on home mechanical ventilation affected by the Philips respironics trilogy ventilator recall

Brandt H, Simon DM, Kasi AS. Ventilator change in children on home mechanical ventilation affected by the Philips respironics trilogy ventilator recall. Pediatr Pulmonol. 2022 Jan;57(1):43-48. doi: 10.1002/ppul.25730. Epub 2021 Oct 21. PMID: 34664797.

• A retrospective study was conducted to review children using home PPV-T with recalled Trilogy ventilators who underwent inpatient ventilator change to non-recalled portable home ventilators (PHV) using our collaborative institutional protocol.

Bronchoscopic interventions for plastic bronchitis in children without structural heart disease

Kallam EF, Kasi AS, Patki R, Silva GL, Simon DM, Caltharp S, Guglani L. Bronchoscopic interventions for plastic bronchitis in children without structural heart disease. Eur J Pediatr. 2021 Dec;180(12):3547-3554. doi: 10.1007/s00431-021-04161-5. Epub 2021 Jun 23. PMID: 34159443.

• This study describes the clinical features, management, and outcomes in our cohort of children with non-structural heart disease-related plastic bronchitis. It was determined that in children without structural heart disease, asthma is a risk factor for recurrent plastic bronchitis. Cryotherapy via bronchoscopy is a safe and effective intervention in patients with refractory plastic bronchitis.

Mortality and Outcomes of Pediatric Tracheostomy Dependent Patients

Hebbar KB, Kasi AS, Vielkind M, McCracken CE, Ivie CC, Prickett KK, Simon DM. Mortality and Outcomes of Pediatric Tracheostomy Dependent Patients. Front Pediatr. 2021 May 4;9:661512. doi: 10.3389/fped.2021.661512. PMID: 34017809; PMCID: PMC8129024.

• This research described clinical factors associated with mortality and causes of death in tracheostomy-dependent (TD) children. In this study, TD children had a high mortality rate with no significant difference in mortality based on indication for tracheostomy. Pulmonary indication for tracheostomy was associated with a shorter time to death, and neurologic indication was associated with lower decannulation rates.

Recent Advances in Pathophysiology and Management of Transient Tachypnea of Newborn

Alhassen Z, Vali P, Guglani L, Lakshminrusimha S, Ryan RM. Recent Advances in Pathophysiology and Management of Transient Tachypnea of Newborn. J Perinatol. 2021 Jan;41(1):6-16. doi: 10.1038/s41372-020-0757-3. Epub 2020 Aug 4. PMID: 32753712.

• New imaging modalities such as lung ultrasound can help in the diagnosis of TTN and early management with distending pressure using continuous positive airway pressure may prevent exacerbation of respiratory distress.