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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Pediatrics".

Deadline for manuscript submissions: closed (25 July 2023) | Viewed by 27590

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Special Issue Editors

Prof. Dr. Lea Bentur

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Guest Editor

1. Pediatric Pulmonary Institute, CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel
2. Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 3109601, Israel
Interests: pediatric respirology; pediatric pulmonology; cystic fibrosis
Special Issues, Collections and Topics in MDPI journals

Dr. Ronen Bar-Yoseph

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Guest Editor

1. Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
2. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Interests: pediatric pulmonology; cardiopulmonary exercise testing; exercise physiology; pediatric origin of adult disease

Special Issue Information

Dear Colleagues,

You are invited to submit a paper for inclusion in a Special Issue of "New Insights into Pediatric Pulmonology" in the Journal of Clinical Medicine. This Special Issue aims to provide a platform for researchers and clinicians to send new research and developments in the field of pediatric pulmonology.

Areas of interest for this Special Issue include the following topics:

Novel methods of functional assessment;
New insights in exercise physiology;
Effect of maturation and puberty on pulmonary parameters;
Translational aspects of overweight and obesity;
Evaluation of active rehabilitation in pediatric pulmonology;
Long-term and post-COVID-19;
Pediatric origin of adult disease.

We sincerely welcome your submission to the Journal of Clinical Medicine.

Prof. Dr. Lea Bentur
Dr. Ronen Bar-Yoseph
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

pediatric pulmonology
exercise testing
COVID-19
cardiopulmonary exercise testing

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Published Papers (11 papers)

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Research

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10 pages, 1499 KiB

Open AccessArticle

Transcutaneous CO₂ Monitoring in Extremely Low Birth Weight Premature Infants

by Liron Borenstein-Levin, Noa Avishay, Orit Soffer, Shmuel Arnon, Arieh Riskin, Gil Dinur, Karen Lavie-Nevo, Ayala Gover, Amir Kugelman and Ori Hochwald

J. Clin. Med. 2023, 12(17), 5757; https://doi.org/10.3390/jcm12175757 - 4 Sep 2023

Cited by 2 | Viewed by 2081

Abstract

Extremely low birth weight (ELBW) premature infants are particularly susceptible to hypocarbia and hypercarbia, which are associated with brain and lung morbidities. Transcutaneous CO₂ (TcCO₂) monitoring allows for continuous non-invasive CO₂ monitoring during invasive and non-invasive ventilation and is becoming more popular in the NICU. We aimed to evaluate the correlation and agreement between CO₂ levels measured by a TcCO₂ monitor and blood gas CO₂ (bgCO₂) among ELBW infants. This was a prospective observational multicenter study. All infants < 1000 g admitted to the participating NICUs during the study period were monitored by a TcCO₂ monitor, if available. For each bgCO₂ measured, a simultaneous TcCO₂ measurement was documented. In total, 1828 pairs of TcCO₂–bgCO₂ values of 94 infants were collected, with a median (IQR) gestational age of 26.4 (26.0, 28.3) weeks and birth weight of 800 (702, 900) g. A moderate correlation (Pearson: r = 0.64) and good agreement (bias (95% limits of agreement)):(2.9 [−11.8, 17.6] mmHg) were found between the TcCO₂ and bgCO₂ values in the 25–70 mmHg TcCO₂ range. The correlation between the TcCO₂ and bgCO₂ trends was moderate. CO₂ measurements by TcCO₂ are in good agreement (bias < 5 mmHg) with bgCO₂ among premature infants < 1000 g during the first week of life, regardless of day of life, ventilation mode (invasive/non-invasive), and sampling method (arterial/capillary/venous). However, wide limits of agreement and moderate correlation dictate the use of TcCO₂ as a complementary tool to blood gas sampling, to assess CO₂ levels and trends in individual patients. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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11 pages, 1663 KiB

Open AccessArticle

Congenital Central Hypoventilation Syndrome in Israel—Novel Findings from a New National Center

by Yakov Sivan, Yael Bezalel, Avital Adato, Navit Levy and Ori Efrati

J. Clin. Med. 2023, 12(12), 3971; https://doi.org/10.3390/jcm12123971 - 11 Jun 2023

Viewed by 1120

Abstract

Background. Congenital central hypoventilation syndrome (CCHS) is a rare autosomal-dominant disorder of the autonomic nervous system that results from mutations in the PHOX2B gene. A national CCHS center was founded in Israel in 2018. Unique new findings were observed. Methods. All 27 CCHS patients in Israel were contacted and followed. Novel findings were observed. Results. The prevalence of new CCHS cases was almost twice higher compared to other countries. The most common mutations in our cohort were polyalanine repeat mutations (PARM) 20/25, 20/26, 20/27 (combined = 85% of cases). Two patients showed unique recessive inheritance while their heterozygotes family members were asymptomatic. A right-sided cardio-neuromodulation was performed on an eight-year-old boy for recurrent asystoles by ablating the parasympathetic ganglionated plexi using radiofrequency (RF) energy. Over 36 months’ follow-up with an implantable loop-recorder, no bradycardias/pauses events were observed. A cardiac pacemaker was avoided. Conclusions. A significant benefit and new information arise from a nationwide expert CCHS center for both clinical and basic purposes. The incidence of CCHS in some populations may be increased. Asymptomatic NPARM mutations may be much more common in the general population, leading to an autosomal recessive presentation of CCHS. RF cardio-neuromodulation offers a novel approach to children avoiding the need for permanent pacemaker implantation. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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11 pages, 509 KiB

Open AccessEditor’s ChoiceArticle

Elevated Neutrophil-to-Lymphocyte Ratio Is Associated with Severe Asthma Exacerbation in Children

by Noga Arwas, Sharon Uzan Shvartzman, Aviv Goldbart, Romi Bari, Itai Hazan, Amir Horev and Inbal Golan Tripto

J. Clin. Med. 2023, 12(9), 3312; https://doi.org/10.3390/jcm12093312 - 6 May 2023

Cited by 9 | Viewed by 2143

Abstract

Asthma is the most common chronic respiratory disease in children. The neutrophil-to-lymphocyte ratio (NLR) is a marker of a chronic inflammatory state; however, data on the association of NLR with acute asthma exacerbations in children is lacking. In this cross-sectional study, between 2016 and 2021, children aged 2–18 years who were referred to the emergency department (ED) due to asthma exacerbation, were included. NLR, calculated from complete blood count upon arrival, was assessed as a continuous variable and was classified into four groups according to quartiles. The association between severity parameters and NLR quartiles was examined. A total of 831 ED visits for asthma exacerbation were included in the study. The median NLR was 1.6, 3.8, 6.7, and 12.9 in quartiles 1–4, respectively (p < 0.001). Demographic parameters, background diseases, and chronic medications were similar between the quartiles. Higher heart rate, body temperature, systolic blood pressure, and respiratory rate were observed in the higher NLR quartiles, as well as lower oxygen saturation. Higher urgency scale and higher rates of intravenous magnesium sulfate were observed in the higher NLR quartiles, with higher admission rates and prolonged hospitalizations. In summary, NLR upon admission is associated with the severity of asthma exacerbation and higher chances of hospitalization among children in the ED. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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7 pages, 1422 KiB

Open AccessArticle

Role of Lung Ultrasonography (LUS) as a Tool for Evaluating Children with Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS)

by Jolanta Tomczonek-Moruś, Natalia Krysiak, Agnieszka Blomberg, Marta Depczyk-Bukała, Marcin Tkaczyk and Krzysztof Zeman

J. Clin. Med. 2023, 12(8), 2850; https://doi.org/10.3390/jcm12082850 - 13 Apr 2023

Cited by 1 | Viewed by 1711

Abstract

Background: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a novel entity. The inflammatory process involves the circulatory, digestive, respiratory, and central nervous systems, as well as the skin. Making a diagnosis requires extensive differential diagnoses, including lung imaging. The aim of our study was to retrospectively assess the pathologies found in lung ultrasound (LUS) in children diagnosed with PIMS-TS and to evaluate the usefulness of the examination in diagnostics and monitoring. Methods: The study group consisted of 43 children diagnosed with PIMS-TS, in whom LUS was performed at least three times, including on admission to hospital, on discharge, and 3 months after disease onset. Results: Pneumonia (mild to severe) was diagnosed in 91% of the patients based on the ultrasound image; the same number had at least one pathology, including consolidations, atelectasis, pleural effusion, and interstitial or interstitial-alveolar syndrome. By the time of discharge, the inflammatory changes had completely regressed in 19% of the children and partially in 81%. After 3 months, no pathologies were detected in the entire study group. Conclusion: LUS is a useful tool for diagnosing and monitoring children with PIMS-TS. Inflammatory lesions of the lungs resolve completely when the generalized inflammatory process subsides. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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12 pages, 2340 KiB

Open AccessArticle

Airway Findings in Patients with Hunter Syndrome Treated with Intravenous Idursulfase

by Richard De Vuyst, Elizabeth Jalazo, Tamy Moraes Tsujimoto, Feng-Chang Lin, Joseph Muenzer and Marianne S. Muhlebach

J. Clin. Med. 2023, 12(2), 480; https://doi.org/10.3390/jcm12020480 - 6 Jan 2023

Viewed by 2683

Abstract

People with Hunter syndrome are known to be affected by a variety of airway pathologies. Treatment of Hunter syndrome with the enzyme replacement therapy (ERT) idursulfase is now the standard of care. However, it is not known how ERT changes the progression of airway involvement. To evaluate this, we performed a retrospective analysis of bronchoscopies performed on children with Hunter syndrome who were part of intrathecal ERT trials. Findings for airway pathology were extracted from bronchoscopy reports and analyses were performed for cross-sectional and longitudinal changes in airway disease. One-hundred and thirty bronchoscopies from 23 subjects were analyzed. Upper airway disease (adenoid hypertrophy and/or pharyngomalacia) was reported in 93% and 87% of bronchoscopies, respectively. Laryngeal abnormalities were recognized in 46% of cases. There were lower airway (tracheal and or bronchial) findings in 64% of all bronchoscopies and prevalence increased with age. Evaluations over time adjusted for repeat evaluations showed that increasing airway involvement was associated with older age (p = 0.0007) despite ongoing ERT. No association was discovered between age of intravenous ERT initiation and progression of airway disease. Individuals with Hunter syndrome who are receiving intravenous enzyme replacement therapy showed the progression of airways disease supporting the need for regular airway monitoring and intervention. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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8 pages, 653 KiB

Open AccessArticle

Lactose-Containing Dry-Powder Inhalers for Patients with Cow’s Milk Protein Allergy—The Conundrum; A National Survey of Pediatric Pulmonologists and Allergologists

by Ophir Bar-On, Hagit Levine, Patrick Stafler, Einat Shmueli, Eyal Jacobi, Ori Goldberg, Guy Steuer, Dario Prais and Meir Mei-Zahav

J. Clin. Med. 2022, 11(24), 7346; https://doi.org/10.3390/jcm11247346 - 10 Dec 2022

Cited by 1 | Viewed by 2324

Abstract

Introduction: Several dry-powder inhalers (DPIs) contain lactose which may be contaminated with milk proteins. Confusion exists pertaining to DPI use in patients with cow’s milk protein allergy (CMPA). Methods: A computerized survey sent via e-mail to pediatric pulmonologists and allergologists. Results: A total of 77 out of 232 (33.2%) doctors replied, of whom 80.5% were pediatric pulmonologists. A total of 69 of 77 (89.6%) were specialists, 37.6% with more than 15 years of experience. The most commonly used DPIs were formoterol + budesonide and vilanterol + fluticasone. A total of 62 out of 77 (80.5%) responders knew these DPIs contained lactose. A total of 35 out of 77 (45.5%) doctors who replied did not know that DPI leaflets list CMPA as a contra-indication to DPI administration. Of these, 4 (11.4%) stated that they would instruct patients with CMPA to stop DPIs, and 7 (20%) would avoid recommending DPIs. A total of 42 out of 77 (54.5%) responders were aware of this warning, yet 13 of these 42 (30.9%) continued to recommend lactose-containing DPIs without hesitation and 18 of these 42 (42.8%) responders prescribed DPIs but considered allergy severity. Conclusions: Almost half of certified, experienced pediatric pulmonologists and allergologists were unaware of the warning to administer DPIs to patients with CMPA. Most doctors who do know of this warning still continue to prescribe these DPIs. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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7 pages, 584 KiB

Open AccessArticle

Reversible Bronchial Obstruction in Primary Ciliary Dyskinesia

by Hagit Levine, Ophir Bar-On, Vered Nir, Nicole West, Yotam Dizitzer, Huda Mussaffi and Dario Prais

J. Clin. Med. 2022, 11(22), 6791; https://doi.org/10.3390/jcm11226791 - 16 Nov 2022

Cited by 5 | Viewed by 1401

Abstract

Background: Inhaled bronchodilators are frequently used among patients with primary ciliary dyskinesia (PCD), although neither the effectiveness nor the prevalence of their use is known, due to the paucity of relevant studies. Methods: This is a retrospective analysis of pre- and post-bronchodilator spirometry results, of patients with PCD from two centers. Correlations were examined of bronchodilator response, with asthma and atopy markers. Results: Of 115 patients, 46 (40%) completed spirometry pre- and post-bronchodilation. Of these, 26 (56.5%) demonstrated reversible airway obstruction (increase in %FEV₁ predicted ≥ 10%). Obstruction reversibility was not found to be associated with a family history of asthma, blood eosinophil level, elevated IgE, or atopy symptoms. Of the 46 patients who completed bronchodilator spirometry, 29 (63%) were regularly using bronchodilators and inhaled corticosteroids. Conclusions: More than half of patients with PCD presented with reversible airway obstruction, without any correlation to markers of personal or familial atopy. Inhaled bronchodilators and corticosteroid therapies are commonly used for treating PCD. Evaluating bronchodilator response should be considered, and its effectiveness should be further studied. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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31 pages, 504 KiB

Open AccessArticle

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group

by Roberto Grandinetti, Valentina Fainardi, Carlo Caffarelli, Gaia Capoferri, Angela Lazzara, Marco Tornesello, Aniello Meoli, Barbara Maria Bergamini, Luca Bertelli, Loretta Biserna, Paolo Bottau, Elena Corinaldesi, Nicoletta De Paulis, Arianna Dondi, Battista Guidi, Francesca Lombardi, Maria Sole Magistrali, Elisabetta Marastoni, Silvia Pastorelli, Alessandra Piccorossi, Maurizio Poloni, Sylvie Tagliati, Francesca Vaienti, Giuseppe Gregori, Roberto Sacchetti, Sandra Mari, Manuela Musetti, Francesco Antodaro, Andrea Bergomi, Lamberto Reggiani, Fabio Caramelli, Alessandro De Fanti, Federico Marchetti, Giampaolo Ricci, Susanna Esposito and on behalf of the Emilia-Romagna Asthma (ERA) Study Group Show full author list Hide full author list

J. Clin. Med. 2022, 11(21), 6558; https://doi.org/10.3390/jcm11216558 - 4 Nov 2022

Cited by 10 | Viewed by 3443

Abstract

Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children’s exposure to risk factors that may permanently affect respiratory health. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

Review

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11 pages, 6961 KiB

Open AccessReview

Challenges in DICER1-Associated Lung Disease

by Kamal Masarweh, Oz Mordechai, Michal Gur, Ronen Bar-Yoseph, Lea Bentur and Anat Ilivitzki

J. Clin. Med. 2023, 12(5), 1918; https://doi.org/10.3390/jcm12051918 - 28 Feb 2023

Cited by 4 | Viewed by 2259

Abstract

Pleuropulmonary blastoma (PPB) is a tumor occurring almost exclusively in infants and young children. This is the most common primary-lung malignancy in childhood. There is age-associated progression through a distinctive sequence of pathologic changes, from a purely multicystic lesion type I to a high-grade sarcoma type II and III. While complete resection is the cornerstone treatment for type I PPB, aggressive chemotherapy with a less favorable prognosis is associated with type II and III. DICER1 germline mutation is positive in 70% of children with PPB. Diagnosis is challenging, as it resembles congenital pulmonary airway malformation (CPAM) in imaging. Although PPB is an extremely rare malignancy, over the past five years we have encountered several children diagnosed with PPB in our medical center. Herein, we present some of these children and discuss diagnostic, ethical, and therapeutic challenges. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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14 pages, 476 KiB

Open AccessReview

Pregnancy in Cystic Fibrosis—Past, Present, and Future

by Michal Gur, Mordechai Pollak, Ronen Bar-Yoseph and Lea Bentur

J. Clin. Med. 2023, 12(4), 1468; https://doi.org/10.3390/jcm12041468 - 12 Feb 2023

Cited by 5 | Viewed by 3122

Abstract

The introduction of mutation-specific therapy led to a revolution in cystic fibrosis (CF) care. These advances in CF therapies have changed the disease profile from a severe incurable disease with limited survival to a treatable disease with improved quality of life and survival into adulthood. CF patients are now able to plan their future, including marriage and parenthood. Side by side with the optimism, new issues and concerns are arising, including fertility and preparation for pregnancy, maternal and fetal care during pregnancy, and post-partum care. While cystic fibrosis transmembrane regulator (CFTR) modulators show promising results for improving CF lung disease, data on their safety in pregnancy are still limited. We performed a literature review on pregnancy in CF from the past, with the first described pregnancy in 1960, through the current fascinating changes in the era of CFTR modulators, to ongoing studies and future directions. Current advances in knowledge give hope for improved outcomes of pregnancy, towards the best possible prognosis for the mother and for the baby. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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Other

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13 pages, 995 KiB

Open AccessCommentary

A Review, Update, and Commentary for the Cough without a Cause: Facts and Factoids of the Habit Cough

by Miles Weinberger, Dennis Buettner and Ran D. Anbar

J. Clin. Med. 2023, 12(5), 1970; https://doi.org/10.3390/jcm12051970 - 2 Mar 2023

Cited by 11 | Viewed by 3520

Abstract

Background: A habitual cough, persisting after the cause is gone, was described in a 1694 medical book. Successful treatment of this disorder known as habit cough was reported in 1966 by the “art of suggestion”. The purpose of this article is to provide the current basis for diagnosis and treatment of the Habit Cough Syndrome. Method: The epidemiology and clinical course of habit cough were reviewed; original data were obtained from three sources. Results: Unique clinical presentation was the basis for diagnosis of habit cough. Diagnosis was made 140 times with increasing frequency over 20 years at the University of Iowa clinic and 55 times over 6 years at a London clinic. Suggestion therapy provided more frequent cessation of cough than just reassurance. A Mayo Clinic archive of chronic involuntary cough found 16 of 60 still coughing 5.9 years after initial evaluation. Ninety-one parents of children with habit cough and 20 adults reported cessation of coughing from viewing a publicly available video of successful suggestion therapy. Conclusions: Habit cough is recognizable from the clinical presentation. It is effectively treated in most children by suggestion therapy in clinics, by remote video conferencing, and by proxy from viewing a video of effective suggestion therapy. Full article

(This article belongs to the Special Issue New Insights into Pediatric Pulmonology)

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