Paediatric airway endoscopy is accepted as a diagnostic and therapeutic procedure, with an expanding number of indications and applications in children. The aim of this European Respiratory Society task force was to produce a statement on interventional bronchoscopy in children, describing the evidence available at present and current clinical practice, and identifying areas deserving further investigation. The multidisciplinary task force panel performed a systematic review of the literature, focusing on whole lung lavage, transbronchial and endobronchial biopsy, transbronchial needle aspiration with endobronchial ultrasound, foreign body extraction, balloon dilation and occlusion, laser-assisted procedures, usage of airway stents, microdebriders, cryotherapy, endoscopic intubation, application of drugs and other liquids, and caregiver perspectives. There is a scarcity of published evidence in this field, and in many cases the task force had to resort to the collective clinical experience of the committee to develop this statement. The highlighted gaps in knowledge underline the need for further research and serve as a call to paediatric bronchoscopists to work together in multicentre collaborations, for the benefit of children with airway disorders.

https://erj.ersjournals.com/content/erj/50/6/1700901.full.pdf

ERS statement: interventional bronchoscopy in children.

The COVID-19 infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue worldwide, as no vaccines or drugs for prevention and treatment have been approved so far, except remdesivir that has been recently authorized for use in the USA and Japan [1]. Many clinical studies are ongoing. Most of them evaluate established antiviral drugs such as lopinavir/ritonavir, and chloroquine (CQ) or its derivative hydroxychloroquine (HCQ), which have shown in vitro antiviral activity against SARS-CoV-2 [2]. Because SARS coronavirus infections are known to induce inflammation and subsequent tissue damage in the lungs in moderate-to-severe cases [3], using immunomodulating drugs could provide a benefit in the treatment of COVID-19. Drugs with the most relevant immunomodulatory profile remain to be found. We believe the antibacterial macrolide azithromycin (AZM) has a special and interesting profile in this search for drug therapy for COVID-19. We discuss below the arguments for this claim. It has been shown that AZM has significant antiviral properties. In contrast with CQ or HCQ, its antiviral activity has been shown in vitro and/or in vivo on a large panel of viruses: Ebola, Zika, respiratory syncytial virus, influenzae H1N1 virus, enterovirus, and rhinovirus [4–13]. Its activity against respiratory syncytial virus has been demonstrated in a randomized study in infants [10]. Azithromycin exhibited a synergistic antiviral effect against SARS-CoV-2 when combined with HCQ both in vitro [11] and in a clinical setting [13]. Of note, the pre-print version of the article from Andreani et al. [14] also reported a significant antiviral effect of AZM alone on SARS-CoV-2. The mechanisms of the antiviral effect of AZM support a large-spectrum antiviral activity. Azithromycin appears to decrease the virus entry into cells [2, 8]. In addition, it can enhance the immune response against viruses by several actions. Azithromycin up-regulates the production of type I and III interferons (especially interferon-β and interferon-λ), and genes involved in virus recognition such as MDA5 and RIG-I [7, 12, 13, 15, 16]. These mechanisms are universally involved in the innate response against infectious agents, and potentially against SARS-CoV-2. The immunomodulation properties of AZM are the rationale of its use against inflammatory manifestations leading to interstitial lung disease [17, 18]. SARS-CoV-2 has been shown to exacerbate the inflammatory response of its host, leading to serious damage of lung interstitial tissue [19]. Patients with severe COVID-19-associated pneumonia may exhibit a syndrome of systemic hyper-inflammation designated as a cytokine storm [20]. Cytokine profiles of patients with severe COVID-19 have been compared to those of patients with moderate forms and have shown a notable increase in some pro-inflammatory cytokines such as interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-17, and tumor necrosis factor-α [19–21]. Therapeutic approaches targeting only IL-6 have been proposed but may be double-edged because the timing of its administration might adversely affect viral clearance [21]. By contrast, AZM shows an interesting immunomodulatory profile by inhibiting several cytokines involved in COVID-19 severe respiratory syndrome. Indeed, AZM regulates and/or decreases the production of IL-1β, IL-6, IL-8, IL-10, IL-12, and IFN-α [10, 22, 23]. Hydroxychloroquine also has immunomodulatory effects, and has been reported to decrease IL-1, IL-2, IL-6, IL-17, IL-22, IFN-α, and tumor necrosis factor [24, 25]. Azithromycin and HCQ both decrease the production of major inflammatory cytokines such as IL-1 and IL-6. However, the different profiles of immunomodulation between the two drugs may be crucial for selecting one of them for the treatment of COVID-19, in relation to the pathogenicity of the virus. Indeed, HCQ may decrease IL-2 levels but not AZM, while AZM may decrease IL-8 levels but not HCQ. * Sylvain Goutelle sylvain.goutelle@chu-lyon.fr

/pdf/azithromycin-for-covid-19-more-than-just-an-antimicrobial-2gmr6br8ts.pdf

Azithromycin for COVID-19: More Than Just an Antimicrobial?

BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited. METHODS: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019-nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019-nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground-glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT-PCR for 2019-nCoV and were discharged. The median time from exposure to a negative RT-PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

Novel coronavirus infection in children outside of Wuhan, China.

The term ‘interstitial lung disease’ (ILD) refers to a group of disorders involving both the airspaces and tissue compartments of the lung, and these disorders are more accurately termed diffuse lung diseases. Although rare, they are associated with significant morbidity and mortality, with the prognosis depending upon the specific diagnosis. The major categories of ILD in children that present in the neonatal period include developmental disorders, growth disorders, surfactant dysfunction disorders, and specific conditions of unknown etiology unique to infancy. Whereas lung histopathology has been the gold standard for the diagnosis of ILD, as many of the disorders have a genetic basis, non-invasive diagnosis is feasible, and characteristic clinical and imaging features may allow for specific diagnosis in some circumstances. The underlying mechanisms, clinical, imaging, and lung pathology features and outcomes of ILD presenting in newborns are reviewed with an emphasis on genetic mechanisms and diagnosis.

/pdf/interstitial-lung-disease-in-newborns-2n07pyvyyr.pdf

Interstitial Lung Disease in Newborns

Immunoglobulin replacement therapy (IGRT) has contributed critically to the management of primary antibody deficiencies (PAD) and the decrease in pneumonia rate. However, despite adequate IGRT and improved prognosis, patients with PAD continue to experience recurrent respiratory tract infections, leading to bronchiectasis and continuing decline in lung function with a severe impact on their quality of life. Moreover, non-infectious inflammatory and interstitial lung complications, such as granulomatous-lymphocytic interstitial lung disease, contribute substantially to the overall morbidity of PAD. These conditions develop much more often than appreciated and represent a major therapeutic challenge. Therefore, a regular assessment of the structural and functional condition of the lung and the upper airways with appropriate treatment is required to minimize the deterioration of lung function. This work summarizes the knowledge on lung complications in PAD and discusses the currently available diagnostic tools and treatment options.

/pdf/the-lung-in-primary-immunodeficiencies-new-concepts-in-4vdtrgtuvb.pdf

The Lung in Primary Immunodeficiencies: New Concepts in Infection and Inflammation.

Interstitial lung disease in children (chILD) is rare, and most centres will only see a few cases/year. There are numerous possible underlying diagnoses, with specific and non-specific treatment possibilities. The chILD-EU collaboration has brought together centres from across Europe to advance understanding of these considerations, and as part of this process, has created standard operating procedures and protocols for the investigation of chILD. Where established consensus documents exist already, for example, for the performance of bronchoalveolar lavage and processing of lung biopsies, these have been adopted. This manuscript reports our proposals for a staged investigation of chILD, starting from when the condition is suspected to defining the diagnosis, using pathways dependent on the clinical condition and the degree of illness of the child. These include the performance of genetic testing, echocardiography, high-resolution CT, bronchoscopy when appropriate and the definitive investigation of lung biopsy, in order to establish a precise diagnosis. Since no randomised controlled trials of treatment have ever been performed, we also report a Delphi consensus process to try to harmonise treatment protocols such as the use of intravenous and oral corticosteroids, and add-on therapies such as hydroxychloroquine and azithromycin. The aim is not to dictate to clinicians when a therapeutic trial should be performed, but to offer the possibility to collaborators of having a unified approach when a decision to treat has been made.

https://thorax.bmj.com/content/thoraxjnl/70/11/1078.full.pdf

European protocols for the diagnosis and initial treatment of interstitial lung disease in children

Chapter 17 – Congenital Lung Disease

21 – Congenital Lung Disease

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European protocols for the diagnosis and initial treatment of interstitial lung disease in children

Chapter 17 – Congenital Lung Disease

21 – Congenital Lung Disease