Pediatrics – Pulmonology
Joint ATS/CDC/ERS/IDSA Guideline Recommends Shorter, All-Oral Regimens for Drug-Susceptible and Drug-Resistant TB
5 Jan, 2025 | 11:30h | UTCIntroduction: This summary outlines new clinical practice guidelines from the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America on updated treatment regimens for tuberculosis (TB) in low-incidence settings. These recommendations build on recent clinical trials, World Health Organization (WHO) guidance, and were developed using the GRADE and GRADE-ADOLOPMENT methodology. The guidelines aim to shorten treatment duration, reduce pill burden, and improve patient outcomes for both drug-susceptible (DS) and drug-resistant (DR) TB, and they apply to settings where mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies are routinely available. A separate news release from CIDRAP highlights the significance of these shorter, all-oral regimens for adults and children. Directly observed therapy (DOT) remains the standard of care.
Key Recommendations:
Four-Month Regimen for DS-TB in Adults:
- For people aged 12 years or older with isoniazid- and rifampin-susceptible pulmonary TB, a new four-month regimen of isoniazid, rifapentine, moxifloxacin, and pyrazinamide (2HPZM/2HPM) is conditionally recommended. This shortened course is based on a large, randomized trial (Study 31/A5349) demonstrating noninferior efficacy compared to the standard six-month regimen (84.6% vs 85.4% cure, respectively), no increase in adverse events, and potential benefits in completion rates. Exclusions include TB meningitis and other complicated forms of extrapulmonary TB, and clinicians should obtain rapid fluoroquinolone susceptibility tests before initiating this regimen.
Four-Month Regimen for DS-TB in Children:
- For children and adolescents aged 3 months to 16 years with nonsevere, drug-susceptible pulmonary TB, a four-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for the initial phase, followed by isoniazid and rifampin, is strongly recommended. Evidence from the SHINE trial showed high success (97.1% vs 96.9%) and similar safety with the shorter course compared to the 6-month regimen. Nonsevere TB generally excludes extensive cavitary disease, advanced extrapulmonary TB, or complicated forms. Close clinical and radiographic follow-up is important to confirm effective cure.
Six-Month BPaL Regimen for Rifampin-Resistant, Fluoroquinolone-Resistant or Intolerant TB:
- For rifampin-resistant (RR) pulmonary TB with resistance or patient intolerance to fluoroquinolones in adolescents aged 14 and older and adults, a six-month all-oral bedaquiline, pretomanid, and linezolid (BPaL) regimen is strongly recommended, replacing much longer regimens that often included injectables. Clinical trials (Nix-TB, ZeNix) demonstrated higher cure rates and lower toxicity with this regimen compared to longer regimens, though vigilance is needed for linezolid-related adverse events (e.g., neuropathy, myelosuppression). Baseline and monthly lab and ECG checks are advised.
Six-Month BPaLM Regimen for Rifampin-Resistant, Fluoroquinolone-Susceptible TB:
- For RR pulmonary TB that remains fluoroquinolone-susceptible in adolescents aged 14 and older and adults, a six-month bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) regimen is strongly recommended over traditional 15-month or longer regimens in patients with MDR/RR-TB. Data from the TB-PRACTECAL trial showed high success rates and fewer serious adverse events. BPaLM is the first-line recommendation for this group. Close monitoring of cardiac status (QTc prolongation) and blood counts is advised.
Both BPaL and BPaLM regimens require detailed drug susceptibility testing and cautious management of potential drug–drug interactions, particularly for patients with comorbidities or HIV infection. Of note, the certainty of evidence for the outcomes in the DR-TB trials was rated as very low, due to multiple factors including bias, small event numbers, lack of blinding, and inconsistent outcomes.
Conclusion: These new recommendations markedly shorten TB treatment courses for adults and children in low-incidence settings with access to appropriate diagnostic tools, while avoiding injectables and reducing serious toxicities. By replacing older, more complex regimens with all-oral, shorter-duration therapy, and using DOT as the standard of care, the guidelines aim to improve adherence, lessen the burden on healthcare systems, and enhance patient quality of life. Ongoing research will further refine dosing, safety for special populations (e.g., pregnant individuals), and the role of advanced drug susceptibility testing.
Reference:
Jussi J. Saukkonen, Raquel Duarte, Sonal S. Munsiff, et al. “Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.” American Journal of Respiratory and Critical Care Medicine, (2025). https://doi.org/10.1164/rccm.202410-2096ST
News release commentary: “New guidelines expand recommendations for shorter, all-oral TB treatments” (CIDRAP). https://www.cidrap.umn.edu/tuberculosis/new-guidelines-expand-recommendations-shorter-all-oral-tb-treatments
RCT: Twice-Yearly Depemokimab Reduced Exacerbations in Severe Eosinophilic Asthma
17 Sep, 2024 | 22:39h | UTCBackground: Severe asthma with an eosinophilic phenotype often leads to frequent exacerbations despite treatment with medium- or high-dose inhaled glucocorticoids and additional controllers. Interleukin-5 is pivotal in eosinophil growth and survival, contributing to airway inflammation. Existing biologic therapies targeting interleukin-5 require frequent dosing intervals. Depemokimab is an ultra-long-acting anti–interleukin-5 biologic with enhanced binding affinity, potentially allowing effective dosing every six months.
Objective: To evaluate the efficacy and safety of twice-yearly depemokimab in reducing exacerbations in patients with severe eosinophilic asthma.
Methods: Two multicenter, randomized, double-blind, placebo-controlled phase 3A trials (SWIFT-1 and SWIFT-2) were conducted. Patients aged ≥12 years with severe asthma and an eosinophilic phenotype (blood eosinophil count ≥300 cells/μL in the previous 12 months or ≥150 cells/μL at screening) and at least two exacerbations in the prior year despite medium- or high-dose inhaled glucocorticoids plus another controller were enrolled. Participants were randomized 2:1 to receive depemokimab 100 mg or placebo subcutaneously at weeks 0 and 26, alongside standard care. The primary endpoint was the annualized rate of exacerbations over 52 weeks. Secondary endpoints included changes from baseline in the St. George’s Respiratory Questionnaire (SGRQ) score, prebronchodilator FEV₁, and asthma symptom scores at 52 weeks.
Results: A total of 792 patients were randomized, with 762 included in the full analysis set (502 depemokimab, 260 placebo). In SWIFT-1, depemokimab significantly reduced the annualized exacerbation rate compared to placebo (0.46 vs 1.11; rate ratio 0.42; 95% CI, 0.30–0.59; P < .001). Similar results were observed in SWIFT-2 (0.56 vs 1.08; rate ratio 0.52; 95% CI, 0.36–0.73; P < .001). No significant between-group differences were found in change from baseline in SGRQ scores. The incidence of adverse events was similar between groups in both trials.
Conclusions: Twice-yearly administration of depemokimab significantly reduced the annualized rate of exacerbations in patients with severe eosinophilic asthma.
Implications for Practice: Depemokimab administered every six months may offer an effective treatment option for reducing exacerbations in severe eosinophilic asthma, potentially enhancing patient adherence and reducing treatment burden associated with more frequent dosing schedules.
Study Strengths and Limitations: Strengths include large, multicenter, randomized, placebo-controlled design and replicate trials confirming efficacy. Limitations involve the lack of significant improvement in quality-of-life measures, low exacerbation rates in the placebo group, potential impact of the COVID-19 pandemic on trial conduct and outcomes, and limited data on certain subpopulations.
Future Research: Further studies are needed to assess long-term safety and efficacy, effects on quality-of-life measures, and the role of depemokimab in broader asthma populations, including those with varying eosinophil counts and biomarker profiles.
Meta-Analysis: Daily Sedation Interruption Shortens PICU Stay Without Impacting Mortality or Ventilation Duration in Pediatric MV Patients – JAMA Netw Open
11 Aug, 2024 | 13:19h | UTCStudy Design and Population: This systematic review and meta-analysis included six randomized clinical trials (RCTs) involving 2,810 pediatric patients receiving mechanical ventilation (MV) in the pediatric intensive care unit (PICU). The trials compared the effects of daily sedation interruption (DSI) with continuous intravenous (IV) sedation on clinical outcomes such as MV duration and PICU length of stay.
Main Findings: The analysis found that DSI was associated with a significant reduction in the length of PICU stay (mean difference of -1.45 days, p = 0.03). However, there was no significant difference in the duration of MV between DSI and continuous sedation (mean difference of -0.93 days, p = 0.06). Additionally, there were no significant differences in total sedative doses, adverse events, or mortality between the two groups.
Implications for Practice: The findings suggest that DSI may reduce the length of PICU stay without increasing the risk of adverse events, making it a potentially valuable strategy in managing sedation for pediatric patients on MV. However, further research is needed to explore the long-term neurodevelopmental outcomes associated with DSI.
RCT: No significant benefit of adjuvant prednisone for patients with cystic fibrosis with exacerbations unresponsive to antibiotics – Eur Respir J
6 May, 2024 | 06:32h | UTCThis randomized, double-blind, placebo-controlled trial investigated the effectiveness of adjuvant oral prednisone in enhancing lung function recovery in patients with cystic fibrosis (CF) experiencing pulmonary exacerbations (PExs) unresponsive to initial intravenous (IV) antibiotic treatment. The study involved 173 participants, with 76 not achieving more than 90% of their baseline forced expiratory volume in one second (ppFEV1) by Day 7 of antibiotic treatment and subsequently randomized to receive either oral prednisone (1 mg·kg−1 twice daily, up to 60 mg/day) or placebo for an additional 7 days. Results showed that 50% of the prednisone group and 39% of the placebo group recovered over 90% of their baseline ppFEV1 by Day 14. However, the difference was not statistically significant (11% difference; 95% CI -11, 34%; p=0.34). Additionally, prednisone did not significantly prolong the time to the next exacerbation compared to placebo. This study concludes that adjuvant oral prednisone does not significantly improve lung function recovery or delay subsequent exacerbations in CF patients not responding to initial antibiotic therapy.
Reference (link to abstract – $ for full-text):
RCT: Azithromycin fails to prevent moderate or severe chronic lung disease in preterm infants – Lancet Respir Med
6 May, 2024 | 06:28h | UTCThis randomized, placebo-controlled trial evaluated the effectiveness of azithromycin in preventing chronic lung disease (CLD) in preterm infants born at less than 30 weeks’ gestation across 28 UK neonatal intensive care units. A total of 799 infants were randomized to receive either intravenous azithromycin or a placebo. The primary outcome measured was survival without moderate or severe CLD at 36 weeks postmenstrual age. Results showed no significant difference between the azithromycin group (42% survival without CLD) and the placebo group (45% survival without CLD), with an adjusted odds ratio of 0.84 (95% CI 0.55–1.29, p=0.43). Pulmonary Ureaplasma spp colonization did not affect the treatment outcome. Given the lack of efficacy and the presence of several serious adverse events in the azithromycin group, the study concluded that azithromycin should not be recommended for preventing CLD in this population.
Reference (link to free full-text):
ERS statement on protracted bacterial bronchitis in children
11 Aug, 2023 | 15:32h | UTCERS statement on protracted bacterial bronchitis in children – European Respiratory Journal
RCT – 2ry analysis | Use of NIPPV, NHFOV post-extubation outperforms NCPAP in neonates with severe respiratory failure or extremely preterm
4 Aug, 2023 | 11:48h | UTC
Commentary on Twitter
2nd analysis of NASONE trial in @JAMANetworkOpen examines whether NHFOV is superior in reducing the duration of IMV in comparison to NIPPV and NCPAP in infants born < 28 weeks https://t.co/oWqvO4E5QF
2022 NASONE study: https://t.co/1rfZpaIseN #EBNEOalerts #neoEBM #neotwitter pic.twitter.com/w3Au8s62K7
— Evidence-Based Neo (@EBNEO) July 5, 2023
Systematic Review | NIPPV potentially superior to NCPAP in reducing reintubation in extubated preterm neonates
4 Aug, 2023 | 11:46h | UTC
M-A | Early NIPPV likely reduces the risk of respiratory failure and intubation in very preterm infants
25 Jul, 2023 | 13:39h | UTC
M-A | Exposure to smoke, overcrowding, poor living conditions, and contact with TB cases identified as risk conditions for pediatric TB
24 Jul, 2023 | 12:43h | UTC
RCT | Preterm infants show same feeding tolerance with NCPAP or HHHFNC
20 Jul, 2023 | 11:01h | UTC
Cohort Study | Intermittent hypoxemia is associated with unfavorable respiratory outcomes in extremely preterm infants
17 Jul, 2023 | 13:28h | UTC
The exposome in respiratory diseases: multiple preventable risk factors from early life to adulthood
27 Jun, 2023 | 13:32h | UTC
Commentary on Twitter
The increasing global burden of respiratory diseases over recent decades raises questions about the lifelong impact of environmental factors during industrialisation and urbanisation. There is a clear need for action in primary and secondary prevention. https://t.co/MFzkETBr2X pic.twitter.com/jp9LYSiSAR
— ERS publications (@ERSpublications) June 20, 2023
Cohort Study | Association of preterm birth with increased asthma and COPD risk in adulthood
26 Jun, 2023 | 00:45h | UTCSummary: This population-based register study investigated the correlation between gestational ages (GA) and obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) in adulthood. The study used registry data from 706,717 individuals born between 1987-1998 in Finland (4.8% preterm), and 1,669,528 individuals born from 1967-1999 in Norway (5.0% preterm). The study observed care episodes of asthma and COPD using nationwide healthcare registers.
The results showed an increased risk of obstructive airway disease in adulthood for those born at <28 or 28–31 completed weeks of gestation. Even after adjustments, the risk remained 2-3 times greater compared to those who were born full term (at 39-41 completed weeks). Additionally, the risk for COPD at age 30–50 was significantly higher for those born at <28 weeks, with an odds ratio (OR) of 7.44. The study also identified that bronchopulmonary dysplasia (BPD) in infancy increased the odds of obstructive airway disease for those born at <28 and 28–31 weeks.
These findings suggest that preterm birth is a notable risk factor for asthma and COPD in adulthood, and this risk was observed across all gestational ages before full term. The study recommends diagnostic vigilance for adults born very preterm presenting with respiratory symptoms. However, the researchers also noted the potential limitations of using registry data, which might include residual confounding from unmeasured confounders and lack of data on certain prenatal or early life factors.
Article: Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries – European Respiratory Journal (free for a limited period)
Commentary on Twitter
In this population-based study of 2.4 million people from Finland and Norway, adults born preterm were at higher risk for asthma and COPD at ages 18–50 years. The risks were observed across all gestational ages before full term in a dose-response manner. https://t.co/bGsAOrwAxV pic.twitter.com/WmCoc6cPu2
— ERS publications (@ERSpublications) June 22, 2023
M-A | HFNC, CPAP, BiPAP prove more effective than conventional oxygen therapy in minimizing pediatric extubation failure
19 Jun, 2023 | 13:35h | UTC
Commentary on Twitter
Study suggests that CPAP, HFNC, and BiPAP were more effective than conventional oxygen therapy for providing postextubation noninvasive respiratory support in a pediatric population. https://t.co/d56eNkP8QP @abusultaneh @RobyKhemaniMD @PALISInet
— JAMA Pediatrics (@JAMAPediatrics) June 5, 2023
Review | Point-of-care thoracic ultrasound in children: new advances in pediatric emergency setting
16 Jun, 2023 | 13:59h | UTC
Cluster RCT | Point-of-care CRP testing cuts antibiotic prescriptions in respiratory illnesses in primary care
1 Jun, 2023 | 11:58h | UTCCommentary: Use of CRP testing reduced antibiotics for respiratory infections, trial finds – CIDRAP
SR | Nasal high flow therapy for primary respiratory support in preterm infants
12 May, 2023 | 13:31h | UTCNasal high flow therapy for primary respiratory support in preterm infants – Cochrane Library
Summary: Nasal high flow therapy for breathing support in preterm babies – Cochrane Library
Commentary on Twitter
Nasal high flow therapy for primary respiratory support in preterm infants – 2023 updatehttps://t.co/6UEnZ8fJRS @AmerAcadPeds @ESPR_ESN pic.twitter.com/yLBcQPPPvS
— Cochrane Neonatal (@CochraneNeonate) May 6, 2023
AAP Policy Statement | Protecting children and adolescents from tobacco and nicotine
4 May, 2023 | 13:43h | UTCProtecting Children and Adolescents From Tobacco and Nicotine – Pediatrics
Clinical Report: Protecting Children and Adolescents From Tobacco and Nicotine – Pediatrics
Commentaries:
Protecting Kids From Tobacco’s Harms: AAP Policy Explained – Health Children
SR | Nebulized hypertonic saline solution for acute bronchiolitis in infants
17 Apr, 2023 | 12:37h | UTCNebulised hypertonic saline solution for acute bronchiolitis in infants – Cochrane Library
SR | Chest physiotherapy for acute bronchiolitis in pediatric patients between 0 and 24 months old
10 Apr, 2023 | 13:32h | UTC
Prematurity and bronchopulmonary dysplasia: what general pediatricians should know
30 Mar, 2023 | 14:12h | UTCPrematurity and BPD: what general pediatricians should know – European Journal of Pediatrics
Guidelines | Management of bronchiolitis in infants
28 Mar, 2023 | 14:47h | UTC
SR | Post-tuberculosis sequelae in children and adolescents
27 Mar, 2023 | 13:16h | UTCPost-tuberculosis sequelae in children and adolescents: a systematic review – The Lancet Infectious Diseases (free registration required)
Cohort Study | Early childhood respiratory infections linked to increased risk of premature respiratory disease mortality in adulthood
20 Mar, 2023 | 13:52h | UTCSummary: The study aimed to determine the link between lower respiratory tract infections (LRTIs) in early childhood and premature adult death from respiratory disease. The study used data from a nationally representative cohort recruited at birth in Great Britain in 1946 and followed participants across eight decades.
After adjusting for multiple markers of childhood social disadvantage and adult smoking, the study found that individuals who had an LRTI by age 2 years were 93% more likely to die prematurely from respiratory disease as adults than those who did not have early childhood LRTI, accounting for one-fifth of these deaths and an estimated 179,188 excess deaths across England and Wales between 1972 and 2019.
However, it is important to note that this observational study cannot establish causality, but rather suggests that early childhood LRTI is a marker of increased risk of respiratory-cause deaths later in life.
News Release: Respiratory disease in early childhood linked to higher risk of death for adults – Imperial College London
Commentaries:
Childhood bronchitis, pneumonia tied to premature respiratory death in adults – CIDRAP
Early childhood lower respiratory tract infection: a key determinant of premature adult respiratory mortality – The Lancet (free registration required)
Commentary from the author on Twitter (thread – click for more)
1/ Great to see the interest in our @TheLancet paper linking lower respiratory tract infections in early childhood to the risk of premature adult death from respiratory disease across Great Britain.
A🧵exploring our study (1/21)
Full paper link below:https://t.co/LlGQJC1wAP
— James P Allinson (@JPAllinson) March 11, 2023