First Case of Primary Ciliary Dyskinesia in GreenlandAuthors: Caroline Nygaard1 MD, Morten Dunø2 Ph.D., Carsten Johan Heilmann3MD, June K. Marthin1 Ph.D., Sarah Nygaard1 BM, Tavs Qvist4 Ph.D., Hanne Lynge Rex3 MD, Kim G. Nielsen1,5 MD, Dr. Med. Sci.Affiliations: 1Danish PCD Centre, Danish Pediatric Pulmonary Service, Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 2Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Denmark.3Medical Department M, Queen Ingrid’s Hospital, Nuuk, Greenland. 4Danish PCD Centre, Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark. 5Institute of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, DenmarkEmails: [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] author: Caroline Nygaard, Adress: Department of Pediatrics and Adolescent Medicine, JMC, Rigshospitalet, Blegdamsvej 9, DK-2100 København Ø, Denmark, Telephone: +4552131414, Fax: +4535456717, E-mail: [email protected] of interest : No conflicts of interestEthical statement: The parents have given written informed consent to the use and presentation of patient data, including photos. Exemption from ethics approval: The Regional Health Research Ethics Committees in the Capital Region in Denmark waived the need for ethical approval of the project (no. F-24062931)Keywords: Primary cilia dyskinesia, Genetics, GreenlandRunning Head: Primary cilia dyskinesia in GreenlandClinical correspondence

Background: Cystic Fibrosis Foundation guidelines recommend human milk (HM) as the ideal source of nutrition for children with CF (cwCF). Despite known pulmonary and nutritional benefits, fewer cwCF ever receive HM compared to the general population. Early nutrition choices are preference-sensitive, yet little is known about the factors that impede or sustain HM feeding among parents of cwCF. Objectives: Explore perceptions and experiences of mothers of cwCF who initiated HM feeding. Methods: Mothers of cwCF aged ≤10 years completed audio-taped, semi-structured interviews describing their experiences with HM feeding. Interviews were transcribed and two researchers independently coded the transcripts and conducted content and thematic analysis using an inductive approach. Results: Participants included 28 mothers who initiated HM feeding. Major themes included 1) the impact of a CF diagnosis on HM feeding plans 2) CF-specific challenges to HM feeding 3) mixed perceptions of the CF team’s support for HM feeding and of the role of formula in CF nutritional care and 4) the benefit of lactation consultants as part of the CF care team. Conclusion: Many parents prioritize HM for their cwCF given the well-established health benefits. However, CF-specific barriers to HM feeding are common and nutritional challenges necessitating fortification add additional barriers to sustained HM feeding efforts. While HM may improve long-term pulmonary outcomes, our findings demonstrate the need for personalized support for mothers desiring to HM feed to facilitate shared decision-making around options to optimize early nutritional status among cwCF.

Assessment of phrenic nerve pacers in a patient with Congenital Central Hypoventilation SyndromeTo the Editor:A 13-year-old patient with Congenital Central Hypoventilation Syndrome (CCHS) was transported to the emergency department following an unwitnessed syncopal event with associated cyanosis. She opened her eyes within a few minutes, her mental status returned to normal, and her oxygen saturation increased back to above 95%. Her parents reported she’s had two or three similar events over the past few months. She was born at 38-week gestation with recurrent central apnea noted immediately after birth. Genetic tests revealed that she was heterozygous for a 36 base pair duplication from nucleotide 729 to 764 of the PHOX2B gene (c 729_764dup36), which encodes an additional 12 alanine residues in the polyalanine tract of the PHOX2B protein (p.Ala244_Ala255dup12). With confirmation of a diagnosis of CCHS1, a tracheotomy was performed, and she was discharged home on positive pressure ventilation. By the end of her first year of life, she was able to be weaned to just mechanical ventilation when sleepy or asleep. At 5 years of age, bilateral phrenic nerve pacers were implanted, and she was successfully decannulated and transitioned from positive to negative pressure ventilation (Avery Diaphragm Pacing System, Avery Biomedical Devices, Inc, Commack, NY. At 7 years of age, she was diagnosed with absence epilepsy and placed on levetiracetam with resolution of her seizures. At 8 years of age, prolonged sinus pauses of up to 6 seconds were documented by an implantable loop recorder, and a cardiac pacemaker was implanted.Vital signs and physical examination in the ED were unremarkable, and neuro, cardiology, and pulmonary consults were obtained. There were no signs of infection; chest x-ray and electroencephalogram were unremarkable. Her cardiac pacemaker was interrogated, and there was no evidence that her cardiac pacemaker had been activated before, during, or after her syncopal episode. A 12-lead electrocardiogram (EKG) was obtained (figure 1). This EKG suggests her phrenic nerve pacemakers are functioning normally, with a set rate of 17 breaths per minute. Approximately every 3.5 seconds, 27 electrical pulses over 1.32 seconds are noted, particularly well seen on leads II, III, aVR, aVL, aVF, and V3-V6. Iron deficiency was noted, and it was subsequently confirmed that she suffered from menorrhagia. Her syncopal episode was judged most likely vasovagal in origin, exacerbated by iron deficiency anemia. Realizing the noteworthy aspects of the case, informed consent was obtained from the patient and her family to publish this case report. This case report is exempt from IRB approval by the New York Medical College Institutional Review Board as per the policy in their manual, “If case reports are not identifiable, there is no need…to contact or to submit any documents to the IRB”.Following the seminal work of Glenn WL, et al 2, diaphragmatic pacing has been utilized in patients with spinal cord injuries or patients with amyotrophic lateral sclerosis3. Some patients with CCHS are being transitioned to ventilation with phrenic nerve pacers, thus permitting tracheostomy closure4.Syncope is not uncommon in patients with congenital central hypoventilation syndrome. Patients with CCHS are at risk for life-threatening cardiac arrhythmia and may sometimes require cardiac pacemakers. Patients being ventilated with phrenic nerve pacers without a tracheostomy, are also at risk for obstructive sleep apnea. Patients with CCHS are prone to fainting, and tilt-table testing confirms they are prone to greater orthostatic decreases in blood pressure than healthy control patients.The artefact due to phrenic nerve pacer discharge in figure 1 has been previously demonstrated in the literature. In 1987, Auerbach and Dobelle reported trans telephonic monitoring of patients with implanted neurostimulators, including a similar figure to ours, using 2 EKG leads5. A similar figure was published in a case report of a patient who developed ventricular tachycardia and cardiac arrest during diaphragmatic pacing, and on polysomnography in a patient with CCHS.In conclusion, a routine EKG may be an easy and quick way to determine if phrenic nerve pacers are functioning properly. Both the frequency and amplitude of phrenic nerve stimulation can be estimated on an EKG.

Asthma is a significant public health concern, particularly in low- and middle-income countries (LMICs), which are predominantly located in regions such as North Africa, sub-Saharan Africa, South, Central, and East Asia, the Middle East, Latin America, the Caribbean, and certain parts of Europe. According to the World Health Organization (WHO), nearly 300 million individuals globally suffer from asthma. Data from the GAN Phase I study indicates that approximately one in ten children are asthmatic, with one in twenty experiencing severe asthma. Moreover, in children, 40% in LMICs have poor asthma control, compared to 19.9% in HICs.(1) It is estimated that 90% of the global burden of asthma is borne by individuals in LMICs, where death rates due to asthma are also the highest.(2) Also, in LMICs, children make up a larger proportion of the population compared to higher-income nations, which results in a correspondingly greater burden for those countries on health services due to childhood diseases. Estimates suggest that high proportion of asthma patients reside in LMICs, its prevalence over the past two decades is only increasing or remaining high, and morbidity-mortality rates associated with the condition are disproportionately higher compared to its counterpart high-income countries (HICs). (3)

Indoor air pollution represents a major health problem in developing countries. Common sources of household contaminants in these settings include gas or wood-fired stoves and ovens, heaters, fireplaces, tobacco smoke, dust mites, pets, mold, insecticides, and cleaning products. The use of biomass fuels or coal for daily activities, such as cooking, heating and lighting, are still common practices among many Latin American countries because of cultural behaviors, geographical conditions and limited access to cleaner energy sources. Inefficient combustion of these substances results in the release of toxic products, mainly nitrogen dioxide (NO2), carbon monoxide (CO), particulate matter (PM) and volatile organic compounds (VOC). Additionally, tobacco consumption is frequent in the region and is a well-known cause of air pollution, while electronic cigarettes have also gained popularity worldwide and are now a new source of airborne chemicals. Exposure to all these substances has been associated with an increased risk of health issues, particularly in children, such as growth impairment, respiratory infections, asthma, reduced lung function, and development of adult lung diseases (e.g., cancer and COPD) (1).

To the editor:

Introduction – Uncontrolled asthma is common in children and is associated with a decline in lung function. Repeated personalised assessments of the reasons for inadequate control should including evaluations of the patients’ surroundings. This can be support by Indoor Environmental Advisors (IEAs). This cohort study aimed to assess the impact on asthma control of routine assessment of children’s home by IEAs. Methods – Children aged 4 to 18 years who had asthma severity grades of 3 to 5 according to Global Initiative for Asthma guidelines were enrolled. Asthma control was evaluated using the standardized Asthma Control Test (ACT) before and 3 months after the IEA visit. Results – We enrolled 15 children with moderate-to-severe asthma. Asthma control improved significantly after the IEA visit (p=0.004). The percentage of children with uncontrolled asthma decreased from 64.3% before IEA visit to 27.3% at 3 months, and none of the patients had 2 exacerbations or more within the 3 months after the visit. IEA identified environmental issues whose remediation could likely contribute to improve asthma control. However, there are still barriers to the implementation of IEA that would be beneficial to remove. Conclusion – Our results support the inclusion of IEA interventions as part of the standard care pathway for children with asthma.

home NIV for children must consider the key role of the interface, in addition to selecting the ventilatory mode and settings. Acceptance and adherence to NIV often depend on the time spent selecting the right mask, as well as on regular and careful attention to preventing and addressing various issues that arise during NIV

last year's publications constitute an important step in the care of children with oSDB. The time has come to abandon the sacrosanct Apnea-Hypopnea Index as the sole marker on which we base all decisions for managing children with oSDB. We are entering a new era where better phenotyping of oSDB in children will enable personalized medicine

While the diagnosis of cystic fibrosis (CF) is often straightforward and reliant on correlation between genetic testing and clinical signs and symptoms, there is a subset where the distinction is not nearly as clearcut. This has previously been reported in patients identified through newborn screening but not meeting full CF diagnostic criteria, earning the label of CF Screen Positive, Inconclusive Diagnosis (CFSPID) instead. A homologous diagnostic category in adults is named CF Transmembrane Conductance Regulator-Related Disorder (CFTR-RD). Through a retrospective chart review, this study reports on a relatively large adult cohort (n=23) that presented to pulmonology clinic at a single center with intermediate or positive sweat chloride tests but non-diagnostic full CFTR gene analysis. Median sweat chloride result was 48 mmol/L, and a majority of the cohort had chronic lung disease with atypical pathogens on sputum culture, including Pseudomonas aeruginosa, non-tuberculous Mycobacteria, Acinetobacter species, amongst others. This clinical picture suggests CFTR dysfunction or similar mechanism in the absence of an identified genetic cause. Alternate chloride channels and their respective genes or candidates of genetic modifiers to the CF-phenotype could be targets of further research in this cohort or similar patients. Such genetic modifiers include loci that have been implicated in inflammation, the CFTR interactome, and/or co-/post-translational modification of CFTR.

Background: The present study aimed to determine whether the use of nasal intermittent positive pressure ventilation (NIPPV) during neonatal endotracheal intubation increases the rate of successful intubation without physiological instability during all intubation attempts. Material and Methods: The present study was designed as a prospective, multicenter, randomized, controlled study conducted with neonates undergoing endotracheal intubation. The infants were assigned randomly to either the NIPPV group or the standard care group. The primary outcome was successful intubation without physiological instability (defined as ≥20% decline in the peripheral oxygen saturation [SpO 2] from pre-intubation value or bradycardia with a heart rate of <100 beats per minute) during all intubation attempts. Results: A total of 150 infants were enrolled (75 for the NIPPV group and 75 for the standart-care group). The infants had a mean postmenstrual age of 32.5 weeks and a median weight of 1552 g at the time of intubation. The incidence of successful intubation without physiological instability during all intubation attempts was significantly higher in the NIPPV group (64%) compared to the standard-care group (42.7%) (p = 0.009). This difference was particularly significant when inexperienced practitioners were involved. In the NIPPV group, the rate of bradycardia and severe desaturation was significantly lower, while the lowest SpO 2 level and the lowest heart rate level were significanlty higher. Conclusion: NIPPV during endotracheal intubation increases the incidence of successful intubation without physiological instability during all intubation attempts in neonates, while reducing the rate of hypoxia and bradycardia.

From Dyspnea to Diagnosis: A Pediatric Case Report on an Unexpected ConditionYotam Ophir, MD1, Marketa Bloomfield, MD, PhD2, Jana Tukova, MD, PhD1Department of Pediatric and Inherited Metabolic disorders, General University Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic.2 Department of Immunology, Motol University Hospital, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.

not-yet-known not-yet-known not-yet-known unknown Background: People with cystic fibrosis (CF) may not expectorate sputum at young ages or while on CFTR modulators. While oropharyngeal swabs are commonly used to test for lower airway pathogens, it is unknown whether Staphylococcus aureus isolated from the oropharynx represents the strain that infects the lungs. Our goal was to determine whether oropharyngeal and sputum isolates of S. aureus are genetically distinct in a cohort of patients with CF. Methods: We obtained historical S. aureus isolates from patients who intermittently expectorated sputum in 2018 and we prospectively cultured S. aureus from oropharyngeal swabs and sputum from subjects with CF between August 2020 - February 2022. We performed short-read whole genome sequencing, determined sequence type, and performed phylogenetic analysis using S. aureus core genome single nucleotide polymorphisms (SNPs). We assigned isolates from a patient to the same strain if they had the same sequence type and differed by ≤ 60 SNPs or the isolates were not disturbed by clade breaker analysis. Results: 36 subjects had S. aureus in ≥1 oropharyngeal swab and ≥1 sputum sample in 2018. In the prospective collection, 31 subjects had synchronous oropharyngeal swab and sputum collections. Although polyclonal infections were detected, sputum and oropharyngeal isolates of S. aureus typically matched the same strain within study subjects, both over the span of 2018 (31/36 patients), and when collected simultaneously from 2020-2022 (29/31 patients). Conclusions: In patients with CF who intermittently produce sputum, oropharyngeal swabs identify S. aureus with genetic and phenotypic similarity to those cultured from sputum.

A Protocol for Treating Atelectasis in the Chronically Ventilated Pediatric PatientEliezer Be’eri MBBCh, Nitay Fraenkel MD, Orit Bartov BSc. MPt. Ped, Noah Eisenberg BPT, Rachelle Lavi B Physio, Ofra Ginat BPT, Ma’ayan Shoffer BPT.Department of Respiratory RehabilitationAlyn Pediatric Rehabilitation HospitalJerusalem, IsraelPresented at the 2nd meeting of the International Society of Pediatric Respiratory Diseases (INSPiRED), 2024.ORCID ID (Eliezer Be’eri): 0000-0003-4935-6000Email addresses of authors:Eliezer Be’eri: [email protected] Fraenkel: [email protected] Bartov: [email protected] Lavi: [email protected] Eisenberg: [email protected] Ginat: [email protected]’ayan Shoffer: [email protected] should be addressed to:Eliezer Be’eri, MDALYN Hospital84 Shmaryahu Levin Street, Jerusalem, Israel 91090Phone: +972 [email protected] words: Atelectasis, physiotherapy, tracheostomy, mechanical ventilationAbbreviated title: Protocol for treating atelectasisTo the editor,Lung atelectasis is an important complication occurring in children and adolescents who are ventilator-dependent due to neuromuscular respiratory failure. It may occur if a “low tidal volume” ventilation strategy is used, as is commonly done to avoid barotrauma when ventilating subjects with parenchymal respiratory failure. However, the patient in respiratory failure due to neuromuscular disease, in contrast to the subject with parenchymal respiratory failure, is primarily at risk for alveolar de-recruitment, rather than barotrauma. Some authorities have therefore advocated using a “high tidal volume strategy” \RL1. In the short term, atelectasis causes ventilation-perfusion mismatch, but if left untreated it may become a focus of recurrent infection and eventual bronchiectasis. When atelectasis is identified, it is therefore essential to re-recruit the atelectatic lung segment as early as possible, prior to the atelectasis becoming permanent.A standardized protocol for treating newly diagnosed atelectasis in ventilator-dependent children has been developed and implemented in the Respiratory Rehabilitation Department of Alyn Pediatric Rehabilitation Hospital in Jerusalem, Israel. The protocol aims to achieve rational medical and physiotherapy (PT) resource management in a stepwise and time-limited manner. The protocol employs the full spectrum of medical and physiotherapy modalities available at Alyn Hospital, including alveolar recruitment by means of prolonged “sigh” inhalations, mechanical inexsufflation (MIE), intrapulmonary percussive ventilation (IPPV), Vest therapy, negative-pressure cuirass ventilation (RTX), “green-bag” manual hyperinflation and bronchoscopy, and is detailed in diagram 1.The initial step is to maximize the ventilator parameters (peak inspiratory pressure (PIP) or tidal volume (Vti), and peak end expiratory pressure (PEEP)) and add a sigh recruitment manoeuvre of 40 cmH2O for 10 seconds every 20 minutes. In our experience, addition of the sigh recruitment maneuver often succeeds in opening the atelectatic segment, and no further therapy is needed. After 24 hours a chest Xray is performed. If no clinical (oxygen saturation above 94% or return to pre-atelectasis baseline) or radiological improvement has occurred, physiotherapy treatments are then added in a stepwise manner every 48 hours. Our initial physiotherapy protocol comprises manual chest vibration and ventilation-enhancement maneuvers combined with patient positioning to enhance postural drainage. Such positioning may be prone, or lying on the side with the atelectatic lung superior, and may include use of an abdominal belt to improve diaphragmatic function. Manual physiotherapy is combined with MIE and either IPPV (for tracheostomized subjects) or Vest therapies (if the subject is using non-invasive positive-pressure ventilation (NIPPV)), all performed three times a day. Whereas the Vest and IPPV achieve secretion mobilization (essentially, shaking secretions free of the tracheo-bronchial wall), MIE performs secretion removal (moving the secretions up the airways towards the pharynx). The protocol aims to combine mobilization and removal modalities synergistically. If no clinical improvement has occurred after 48 hours, the physiotherapy modality is changed to use of a negative-pressure cuirass (RTX) in secretion removal mode. Our rationale in choosing this technique is that during negative-pressure ventilation, chest wall expansion occurs in a manner that is morphologically different from the manner in which the thorax expands during positive-pressure ventilation, reflecting the difference between “inflating” the lungs from within versus expanding the chest wall from without. We postulate that this morphological difference manifests also at the level of the airways, meaning that there may be differences between positive-pressure and negative-pressure ventilation in terms of how airways physically expand when exposed to these two modalities. If that is in fact true, negative-pressure ventilation may succeed in achieving alveolar recruitment when positive-pressure ventilation has failed to do so. Indeed, in our experience we have witnessed successful recruitment of an atelectatic segment within 24 hours of initiating negative-pressure ventilation, in cases in which the initial positive-pressure ventilation combined with secretion-mobilization methodologies for 72 hours had failed to achieve such. In particularly resistant cases we have also combined RTX ventilation with simultaneous and synchronous positive-pressure ventilation.In children younger than 2 years of age it may be difficult to successfully fit a negative-pressure cuirass to a small thorax, which precludes using that therapy as a next step after failure of first-line PT techniques. In such circumstances, we employ a technique for achieving prolonged lung insufflation using an anesthesiology “green bag” manual resuscitator. In this technique, a slow, prolonged inspiration with a sustained inspiratory pause is followed by rapid release during the expiratory phase. As small children generally still have a pliable chest wall, this technique can often be effective in achieving sustained and high PEEP levels, encouraging alveolar recruitment.We reserve bronchoscopy for those cases in which no ongoing improvement has been achieved after one week of recruitment-enhancing therapies. This is due to a combination of the invasiveness of the procedure with the low likelihood (in our experience) that bronchoscopy alone will achieve re-expansion of an atelectatic lung segment (unless such atelectasis has been caused by a solid, aspirated foreign body that can be removed).In summary, the described protocol is a pathway for opening a newly diagnosed atelectasis in a chronically ventilated child, in a manner that maximizes the number of potentially beneficial treatment modalities employed in a time-limited and rational framework.Abbreviations:PT: physiotherapyMIE: mechanical inexsufflationIPPV: intrapulmonary percussive ventilationNIPPV: non-invasive positive-pressure ventilationRTX: negative-pressure cuirass ventilationPIP: peak inspiratory pressureVti: inspired tidal volumePEEP: peak end expiratory pressure

Wheeze is the musical continuous sound produced by oscillations in any critically narrowed airways, and heard mostly on expiration. It is common in preschool age, about half of all children will experience an episode of wheezing by their sixth birthday. Asthma is usually characterized by cough, wheeze, chest tightness and fast breathing. It is a significant global health issue and affects both children and adults. The prevalence is on the increase, especially in LMIC. Studies from different populations have revealed the key role influencing the progression from preschool wheezing to childhood asthma. Recurrent wheezing is four or more episodes in the preceding year and has a spectrum of phenotypes and with heterogeneous features. Phenotypes of wheezing were proposed to facilitate the identification of young children who are at risk of subsequent development of asthma. The epidemiology and environmental determinants of recurrent wheezing and asthma are discussed.

not-yet-known not-yet-known not-yet-known unknown Pneumonia is an infection affecting the lower airway, where the air sacs are filled with mucus and pus; and typically presents with cough, fever, and fast breathing. Pneumonia is estimated to be the leading cause of mortality in children under five worldwide with 120 million episodes result in one million deaths globally. 1 The Low-Income and Middle-Income Countries (LMICs) are more affected. In a study in southeast Nigeria, 2 bronchopneumonia accounted for 41.9%, of the cases admitted in the tertiary hospitals and in another hospital based study among children, 3 pneumonia had the highest respiratory admission rates at 34.0%. Pneumonia can be caused by various organisms: Bacterial (Streptococcus, staphylococcus etc), Viral (RSV) and recently COVID 19 pneumonia. RSV has been noted globally to be a major cause of childhood lower respiratory tract infection, with morbidity/mortality occurring in 99% of (LMICs). 4 Some of the long term sequalae are discussed

TITLE: Post-infectious bronchiolitis obliterans in children after the end of the COVID-19 pandemic.To the Editor,Bronchiolitis obliterans (BO) is a rare disease in which the main characteristic is chronic obstruction of the small airways. Post-infectious is the most common cause in children, mainly due to adenovirus (ADV), followed by other viruses such as respiratory syncytial virus (RSV), influenza or parainfluenza. Histologically, inflammation and fibrosis of the terminal bronchioles occurs, with total or partial obliteration of their lumen. The diagnosis of post-infectious bronchiolitis obliterans (PIBO) relies on a compatible clinical history of previous respiratory infection, usually severe, followed by chronic symptoms such as cough, tachypnea, intercostal retractions, hypoxemia and/or pathological auscultation with bilateral or unilateral fine crackles. Computed tomography (CT) of the lungs shows signs of mosaic perfusion pattern, with or without bronchiectasis, and pulmonary function tests with fixed airflow obstruction1. Treatment consists of a combination of anti-inflammatory drugs, oxygen therapy, bronchodilators, respiratory physiotherapy and antibiotics in case of acute infections2.Different authors have described their PIBO cases, highlighting ADV as the main microorganism involved. The highest incidence and prevalence are found in different South American countries with an Amerindian population, such as Argentina, probably related to the presence in these individuals of a characteristic HLA haplotype (DR8-DQB1*0302). The prevalence of PIBO reported in patients developing the disease with severe pneumonia was 30.3% in the province of Jilin, China, after an epidemic outbreak of ADV that occurred in the period from 2018 to 20203. To date, the increase in the number of PIBO cases after the end of the COVID-19 pandemic and the lockdown measures imposed to stop its spread remains unpublished for any geographic area.The epidemiological, etiological, clinical, diagnostic and evolutionary characteristics of 18 pediatric cases with PIBO over a period of 15 years in our center (January 2008 to January 2023) are described. Using the Shapiro-Wilk test, we described quantitative variables as mean and standard deviation (SD) when having a normal distribution, and median and interquartile range (IQR) if they corresponded to non-parametric variables.Of 18 patients diagnosed with PIBO, most are male (67%) and Caucasians (90%). Regarding the causal infection, it occurred at a median age of 1.76 years (IQR 0.96-3.02), with the time interval between October 2022 and January 2023 having the highest number of cases (10 cases) (Figure 1). The most frequent symptoms were cough (100%), fever (94%) and respiratory distress (94%); 100% were diagnosed with bronchitis and 71% with bronchitis and pneumonia. In 11 cases (61%) ADV was isolated as a causal agent, and in the remaining 7 cases ADV could not be confirmed (not analyzed in 5 and unknown in 2). The most frequent findings on chest radiography were pulmonary hyperinflation with unilateral (47%) or bilateral (33%) infiltrate. Hospital admission was required in 94%, out of which 11% were serious infections admitted to the Intensive Care Unit (ICU). Hospitalization time was 9 days (IQR 6.3-14.8 days). Treatment of acute infection was with short-acting beta2-agonist (SABA) nebulization (100%), systemic corticosteroids (SCS) (79%), antibiotics (93%) and oxygen therapy (93%). Two patients required non-invasive mechanical ventilation and 1 endotracheal intubation with invasive mechanical ventilation (IMV).The characteristic clinical history (persistent obstructive respiratory symptoms after a severe infectious condition) and typical radiological findings (mosaic perfusion pattern on CT of the lungs) is the basis for diagnosis. The median age at diagnosis was 3.10 years (IQR 1.89-6.34), with a median time between the causal infection and diagnosis in the entire sample of 1.21 years (IQR 0.65-3.38) and of those infected in 2022-23 of 0.65 years (IQR 0.48-0.78). The most frequent clinical finding after the acute infection was persistent pathological lung auscultation (89%) and recurrent bronchitis (61%). All cases showed a mosaic perfusion pattern on CT of the lungs, 83% bilateral and 17% unilateral (Swyer-James syndrome). A valid forced spirometry test was possible in 56%, all of them showing an obstructive airflow pattern defined by a Z-Score lower than –1.64 (lower limit of normality) of the forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (FEV1/FVC ratio). The mean Z score (±SD) values of forced spirometry are FVC -1.75 (±1.59); FEV1 -3.25 (±1.22); FEV1/FVC -2.66 (±0.59); and the forced expiratory flow at 25-75% (FEF25-75%) is -3.34 (±0.68). The maintenance treatments they received are inhaled corticosteroids (ICS) (28%); ICS with long-acting bronchodilators (LABA) (56%), oral azithromycin (56%); leukotriene-receptor antagonist (78%); SABA rescue inhalers (100%) and 11% do not receive any maintenance treatment. The median course of the disease is 1.30 years (IQR 1.21-8.18).In summary, most cases with PIBO diagnosed in our center had the causal infection with less than 2 years of age, with ADV being the main virus involved, isolated or in coinfection with other viruses such as RSV. Seventeen patients required hospital admission and the most common diagnosis was bronchitis with bilateral pneumonia. Two patients required admission to the ICU due to severe respiratory failure, one of them requiring orotracheal intubation. The basis of the diagnosis is persistent symptoms after the initial infectious condition, supported by the involvement of ADV and an obstructive pattern in spirometry. CT of the lungs with mosaic perfusion pattern served as diagnostic confirmation in all patients. No lung biopsy was required in any of them. The time from the initial injury to the diagnosis of PIBO in our series is approximately 1 year with a disease progression time of 1.3 years. The treatments used, the most in the chronic phase, are ICS with or without LABA, montelukast and oral azithromycin. Only one patient currently requires home oxygen therapy (Table 1).The authors would like to highlight the significant increase in the number of pediatric cases of PIBO in our geographical area, the Autonomous Community of Aragón (Spain), during the months of October 2022 to January 2023 after the end of health restrictions for the recent COVID-19 pandemic. This phenomenon to our knowledge in not published or documented by other authors. Of the 18 cases, 7 had the initial infection related to ADV during this period, and in 2 patients the involvement of ADV is unknown. We are unable to demonstrate in our center an increase in the incidence of serious ADV infections after the COVID-19 pandemic. Regardless, we believe that, as has happened with other microorganisms such as Streptococcus pyogenes group A4 or RSV5, the end of COVID-19 restrictions has led to the appearance of more aggressive infections, in atypical epidemic seasons, a phenomenon known as “immunity debt”6. A recent hypothesis is that children born during the COVID-19 pandemic, where there was a clear decrease in the circulation of viruses, lowered physiological development of immunity due to minimal contact with these infectious agents. After returning to “normality”, the usual infections have appeared in greater numbers and aggressiveness. Analyzing the subgroup of patients infected after the pandemic, all of them were born during the lockdown periods (2020-2022), the disease began at an age of 1.35 years, and the time until diagnosis was shorter than in the total number of patients, 0.65 years. Another interesting fact extracted from our series is that, unlike what other authors describe, most of our patients did not require oxygen therapy for more than 60 days, so we believe that this criterion is not essential for the diagnosis, relying more on other variables such as persistent pathological lung auscultation and subsequent severe bronchitis.

not-yet-known not-yet-known not-yet-known unknown Objective: To investigate the prevalence of clinical manifestations of post COVID-19 condition, also known as long COVID, in children hospitalized with COVID-19. Methods: This is a systematic review of observational studies. We conducted the search on the databases of PUBMED and EMBASE (up to March 15, 2023). We used the following search strategy: ”long COVID” OR ”post COVID-19” OR ”post-acute COVID-19” OR ”long-term COVID” OR ”COVID-19 sequelae” OR ”persistent COVID-19” OR ”chronic COVID-19”. We included observational studies (case-control, cross-sectional, cohort, or case series) that investigated the clinical manifestations of post COVID-19 condition in children (<18 years) admitted with COVID-19. We used the WHO case definition of post COVID-19 condition (ICD-10 U09). Four authors independently assessed the studies. We performed the meta-analysis of prevalence using a random-effects model. Results: Eleven studies involving 2279 patients were included. In the period between ≥3 months and <12 months after acute COVID-19, the most frequent symptom was exercise intolerance with a pooled prevalence of 29% (95% CI: 7-57%), followed by nonspecific respiratory symptoms (12%, 95% CI: 0-48%) and nonspecific gastrointestinal symptoms (10%, 95% CI: 0-37%). In the period ≥12 months after the initial infection, the pooled prevalence of post COVID symptoms was lower, with 6% (95% CI: 2-10%) for exercise intolerance and 3% (95% CI: 0-8%) for fatigue. Conclusions: Clinical manifestations of post COVID condition in hospitalized children include symptoms across multiple organ systems, with higher prevalence in the period up to 12 months after the acute phase of COVID-19.