{"id":7524,"date":"2025-10-08T12:13:23","date_gmt":"2025-10-08T09:13:23","guid":{"rendered":"https:\/\/www.aretaeio.com\/?p=7524"},"modified":"2025-10-08T12:16:08","modified_gmt":"2025-10-08T09:16:08","slug":"bronchiolitis-recent-advances","status":"publish","type":"post","link":"https:\/\/www.aretaeio.com\/en\/bronchiolitis-recent-advances\/","title":{"rendered":"Bronchiolitis Recent Advances"},"content":{"rendered":"

October 2024 Cyprus – Cyprus Pediatrics Society Presentation<\/strong><\/p>\n\n\n\n

Spyros D Pipis MBChB (Hons), DCH, MRCP, FRCPCH, DM, CCST.<\/strong><\/strong><\/p>\n\n\n\n

Clinical Professor of Pediatrics University of Nicosia Medical School Consultant Pediatrician Specialist in Respiratory Pediatrics.<\/strong><\/strong><\/p>\n\n\n\n

Introduction<\/h1>\n\n\n\n

Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children worldwide. It is associated with substantial morbidity and mortality. Estimates suggest that more than 30 million cases of bronchiolitis occur annually with 3.2 million hospitalizations and 120.000 deaths each year. Infants younger than C months <\/em>have the highest disease burden accounting for 40% of all RSV hospitalizations (the majority during the first 3 months<\/strong>). Infants younger than 6 months accounted for 50% of RSV related deaths. Bronchiolitis is the leading cause of infant hospitalizations in high income countries. Death occurs disproportionately in low-income countries (LMIC). LMIC countries have the highest burden of mortality with more than 97% of deaths due to RSV worldwide (more than 70% of these occurring outside the hospital due to insufficient awareness among other factors). Bronchiolitis is the second most common cause of death in infancy after Malaria in LMIC countries.<\/p>\n\n\n\n

Definition<\/h1>\n\n\n\n

There has been a lack of consistency in the definition of bronchiolitis. Although diagnosed on clinical criteria these criteria differ from region to region. Consistency is lacking with respect to age (<12 months or < 24 months), presence of examination findings for example associated with or without wheeze etc. This results in heterogeneous collection of phenotypes grouped under bronchiolitis. An internationally agreed definition is very important.<\/p>\n\n\n\n

Epidemiology<\/h1>\n\n\n\n

Bronchiolitis accounts for 17% of all hospitalizations in children younger than 2 years. In infants less than 6 months 55% of hospital admissions are due to RSV<\/strong>. 5-10% of RSV infected children will progress lower respiratory tract infection and 10% of those will need hospitalization. In Europe during the first year of life 1in 56 of all infants require hospitalization<\/strong>. Among those hospitalized 4-6% need ICU support. Almost 100% of all children aged 2 have been infected with RSV. RSV accounts for 85% of all bronchiolitis cases.<\/p>\n\n\n\n

Other viruses can also lead to disease: Rhinovirus, Human Metapneumovirus, Adenovirus, Parainfluenza and Influenza viruses. These can be present as co infections with RSV as well. Typically, there is seasonal variability as RSV favors cool temperatures and high humidity.<\/p>\n\n\n\n

Pathophysiology<\/h1>\n\n\n\n

Expression of pro inflammatory cytokines with subsequent parabronchial infiltration by neutrophils and lymphocytes. This leads to distal bronchial inflammation and obstruction <\/strong>leading to lung hyper expansion, increased mucous production and oedema.<\/p>\n\n\n\n

Clinical presentation<\/h1>\n\n\n\n

Although there are no pathognomonic clinical signs bronchiolitis manifests primarily with upper respiratory symptoms such as rhinorrhea and cough with or without fever as prodromal symptoms. 4 to 6 days after this, signs of increased breathing effort accompanied by retractions\/recessions, tachypnoea, wheezing and feeding difficulties appear<\/strong>. Children with severe clinical progression can have anorexia, lethargy or irritability, apnoea and hypoxemia indicating the need for hospitalization<\/strong>. One of the major challenges facing clinicians is to predict who will progress towards severe disease. There are no standardized methods to assess RSV severity. Multiple scoring systems have been suggested but none is universally implemented and most lack validation.<\/p>\n\n\n\n

The most important identified risk factor <\/strong>associated with progression to severe disease is gestational age less than 37 weeks, age at presentation less than 10 weeks, exposure to cigarette smoke, poor nutrition, chronic lung disease, congenital heart disease, Cystic Fibrosis, Immunodeficiency, Downs syndrome, Central Hypotonia and poor socioeconomic status. These high-risk factors are additive, and the clinician should have a low threshold for hospital admission in their presence.<\/p>\n\n\n\n

Confirming RSV infection is important and advances in RSV testing in recent years including point of care testing which is rapid and affordable a with a sensitivity and specificity that is non inferior to PCR testing is very important. This may help with cohorting and less antibiotic use.<\/p>\n\n\n\n

Hospital management<\/h1>\n\n\n\n

Supportive care by fluid dehydration and respiratory support are the foundations of evidence- based in hospital management for bronchiolitis. There is no evidence-based therapy for RSV infection.<\/p>\n\n\n\n

With worsening respiratory distress children are unable to maintain oral hydration so in hospital hydration with nasogastric or isotonic intravenous fluids is necessary. Minimal handling is important. The incidence of bacterial co infection is lower than 11% yet a third of children are treated unnecessarily with antibiotics. The decision to use antibiotics should not be based on elevated CRP alone but should also include other indicators of serious bacterial infection such as Procalcitonin level, neonatal age and deterioration while ventilated. The use of CXR is not recommended as a routine investigation particularly in the absence of fever or significant hypoxemia. Infants undergoing CXR are at least 10 times more likely to receive antibiotics.<\/p>\n\n\n\n

Oxygen therapy is the cornerstone of RSV management. An evidence-based threshold of 90% oxygen saturation for Oxygen supplementation has been established now. Lack of long-term adverse outcomes for lower oxygen levels (as low as 88%) is supported by a recent systemic review. High flow nasal cannula (HFNC) has been increasingly used in the past decade for management besides low flow standard oxygen therapy. Recent RCTs show high rates of PICU admission and increased need for mechanical ventilation. It is therefore not recommended.<\/p>\n\n\n\n

Superficial (not deep) suctioning is recommended to clear the nares given the infants are obligatory nasal breathers.<\/p>\n\n\n\n

A recent Cochrane review of 12 clinical trials concluded that none of the Physiotherapy techniques used showed a reduction in the severity of disease. This should only be spared for children with comorbidities like Spinal Muscular Atrophy who have difficulty clearing secretions.<\/p>\n\n\n\n

Nebulized hypertonic saline (3%) is a potentially attractive therapy due to its ability to reduce airway oedema and improve mucus clearance. There is, however, heterogeneity between studies and recent reanalysis do not support a benefit. Large multicenter trials are needed to answer this important question.<\/p>\n\n\n\n

The use of bronchodilators varies by country and region. International guidelines do not recommend their use. A recent Cochrane review found no significant effect. Its possible effect reported by some studies may be due to poor definition of bronchiolitis and may refer to Viral induced Bronchospasm. It is therefore not recommended treatment<\/p>\n\n\n\n

The use of Magnesium Sulfate is also not associated with any improvements and not recommended.<\/p>\n\n\n\n

Several large clinical trials have examined the benefit of oral or inhaled steroids treated in the emergency department and showed no significant effect in reducing admission to the hospital. It is therefore not recommended.<\/p>\n\n\n\n

A multicenter Randomized Controlled study (RCT) found a synergistic effect when nebulized Adrenaline is combined with oral steroids with a 35% relative reduction in hospitalization rate and improvement in symptoms. This has just showed a sight statistical significance. It is perhaps the only treatment that potentially can be recommended. A larger multicenter study is currently underway in Australia, Canada, USA, evaluating whether this treatment regimen reduces hospital admission.<\/p>\n\n\n\n

Today no clear clinical benefit of antivirals has been documented. A nebulized antiviral ALX-0171 was shown to reduce RSV in nasal samples without corresponding clinical benefit suggesting that the immune response that leads to the pathophysiological features discussed above occurs earlier in the disease process that can not be modified by RSV antivirals. Ribavirin is not recommended due to potential teratogenic effects and potential hematological toxicity.<\/p>\n\n\n\n

Despite two decades of messaging that less treatment is better and promoting supportive rather than interventional therapy, de-implementation of interventional therapy <\/strong>in bronchiolitis has not occurred. This remains a major challenge. It is crucial for clinicians to provide all infants with bronchiolitis with the best evidence-based care.<\/p>\n\n\n\n

Long term effects<\/h1>\n\n\n\n

Early life RSV infection is associated with long term respiratory sequelae. It may predispose to recurrent LRTI of any cause. The relationship between RSV and asthma is complex, including genes by viral interactions, host genetic and viral genetic interactions. These can explain the variable susceptibility to asthma following RSV infection. Early premorbid abnormal lung function may predispose to severe RSV Bronchiolitis. RSV bronchiolitis may lead to further lung function impairment even in the presence of a normal premorbid lung function. This leads to post bronchiolitis wheezing syndrome.<\/p>\n\n\n\n

The full public health value of RSV prevention is greater <\/strong>than the health effects measured by prevention of acute early severe bronchiolitis alone. These include reduction of recurrent pneumonias (role of co infection with Influenza or Adenovirus and Pneumococcus, possibly asthma, recurrent wheezing, and lung function impairment. Primary prevention strategies by vaccination may have a significant role in preventing long term respiratory morbidity.<\/p>\n\n\n\n

Prevention<\/h1>\n\n\n\n

Based on our recent experience with COVID-19 pandemic, nonpharmacological preventive measures can be very important. Transmission in households occurs through school aged children and adolescents. Physical distancing, use of face mask, and hand washing reduce RSV circulation. During the pandemic the RSV infections were dramatically reduced due to the above measures.<\/p>\n\n\n\n

The recent approval of not one but 2 vaccines against RSV infection is exciting news and can be<\/strong><\/strong><\/p>\n\n\n\n

characterized as \u201cgame changer\u201d<\/strong><\/strong><\/p>\n\n\n\n

The primary focus of RSV vaccine research has been the RSV surface prefusion (preF) glycoprotein since the epitopes are stable leading to neutralizing antibodies. In 2023 Nirsevimab an extended half-life monoclonal Antibody (mAb) against preF received market approval in Europe and the USA for all infants. The MELODY<\/p>\n\n\n\n

trial showed 74.5 efficacy up to 150 days against medically attended RSV LRTI <\/strong>in healthy preterm and term infants. Thus, allowing improved protection over an entire RSV season with a single injection. First year real life effectiveness against RSV hospitalization is as high as G6% in Spain<\/strong>. The implementation strategy was by administering the injection to all babies born late September to February. (A catch-up group of babies up to 6 months already born outside the bronchiolitis season and high-risk children below aged 2 years were also included). Other mAbs are on the horizon including ones based on mRNA technique.<\/p>\n\n\n\n

Vaccinating pregnant women is an alternative strategy for protecting infants against RSV. A bivalent prefusion protein F vaccine is also approved in 2023. This is given between 24-36 weeks gestation (some countries recommend administration at 28-36 others 32-36 weeks due to a signal of premature births). This led to an efficacy in preventing severe RSV LRTI of 82.4% within the first G0 days of life and 70% within 180 days. <\/strong>(MATISSE study) Real life implementation data are available from Argentina and the effectiveness data have very recently been published with very satisfactory similar results (BERNI study).<\/p>\n\n\n\n

The choice of which vaccination strategy to follow in each country depends on several factors such as the vaccine cost, the infrastructure, The National Health System, cultural factors etc. The important point is that even though the burden of the disease is highest in LMIC the availability of these vaccines in those regions may be a difficult task due to several factors. (Huge mismatch between burden and disease availability\/Inverse law)<\/p>\n\n\n\n

Ideally RSV prevention should target all infants <\/strong>since the majority of hospitalized children with bronchiolitis were healthy full-term babies. At a minimum child at high risk may be an interim strategy in LMIC until universal RSV prevention is widely available.<\/p>\n\n\n\n

A practical suggestion re vaccination strategy in Cyprus.<\/h1>\n\n\n\n

I suggest a combined vaccination implementation strategy:<\/p>\n\n\n\n

I strongly believe that RSV prevention is important to be implemented in Cyprus. For this to be successful it is important to raise public awareness <\/strong>and our professional society being strongly involved in this campaign alongside the Ministry of Health. It is extremely important to have the media involved with exposure to social media as well.<\/p>\n\n\n\n

Maternal vaccination to be offered year-round or preferably in pregnancies that the expected birth would be between November and March. The vaccine has recently been approved and is available in Cyprus at 32-36 weeks of gestation. It is given by the personal Doctor. My suggestion is for the vaccine to be also available and given by the obstetrician. This will hopefully increase uptake<\/p>\n\n\n\n

If parents after discussion with their obstetrician and\/or midwife decide against vaccination during pregnancy (32-36 weeks) babies to be offered mAb during first 1 week of life (see below) if born between end of October and end of February, the bronchiolitis season. If born outside this period and are less than 8 months before the bronchiolitis season to have the mAb administered during October as catch up. If the maternal vaccination was given at a time that the baby was born outside the bronchiolitis season (i.e. the maternal vaccine was administered outside the months of August to February) then monoclonal antibody should be administered as catch up( some countries recommend only to the High-Risk group infants that are born to those pregnancies). High risk group infants (up to aged 2 years) to be offered mAb on two consecutive bronchiolitis seasons.<\/p>\n\n\n\n

A detailed protocol should be agreed between the Ministry of Health and the Cyprus Paediatric Society before officially starting the implementation of this preventative strategy.<\/p>\n\n\n\n

Further reading:<\/p>\n\n\n\n

S S Dalziel, et al Bronchiolitis Seminar the Lancet July 2002<\/p>\n\n\n\n

N I Mazur, et al Respiratory Syncytial Virus 2024 1 Series the Lancet Sept 2024 H J Zar et al Respiratory Syncytial Virus 2024 2 Series the Lancet Sept 2024<\/p>\n\n\n\n

L. L. Hammit et al MELODY study New England Journal of Medicine (NEJM ) March 2022.<\/p>\n\n\n\n

B. Kampmann et al MATISSE study NEJM April 2023<\/p>\n\n\n\n

P M Gonzalo et al BERNI study The Lancet Infectious Diseases May 2025<\/p>","protected":false},"excerpt":{"rendered":"

October 2024 Cyprus – Cyprus Pediatrics Society Presentation Spyros D Pipis MBChB (Hons), DCH, MRCP, FRCPCH, DM, CCST. Clinical Professor of Pediatrics University of Nicosia Medical School Consultant Pediatrician Specialist in Respiratory Pediatrics. Introduction Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children worldwide. It is associated […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"slim_seo":{"title":"Bronchiolitis Recent Advances - \u0391\u03c1\u03b5\u03c4\u03b1\u03af\u03b5\u03b9\u03bf \u039d\u03bf\u03c3\u03bf\u03ba\u03bf\u03bc\u03b5\u03af\u03bf","description":"October 2024 Cyprus - Cyprus Pediatrics Society Presentation Spyros D Pipis MBChB (Hons), DCH, MRCP, FRCPCH, DM, CCST. Clinical Professor of Pediatrics Universi"},"_slim_seo_primary_term_category":0,"_slim_seo_primary_term_post_tag":0,"footnotes":""},"categories":[89],"tags":[],"class_list":["post-7524","post","type-post","status-publish","format-standard","hentry","category-arthra"],"meta_box":[],"_links":{"self":[{"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/posts\/7524","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/comments?post=7524"}],"version-history":[{"count":1,"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/posts\/7524\/revisions"}],"predecessor-version":[{"id":7525,"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/posts\/7524\/revisions\/7525"}],"wp:attachment":[{"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/media?parent=7524"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/categories?post=7524"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.aretaeio.com\/en\/wp-json\/wp\/v2\/tags?post=7524"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}