Mark Everard

• MB ChB DM
• Professor Emeritus at The University of Western Australia

In contrast to significant declines in deaths due to lung cancer and cardiac disease in Westernised countries, the mortality due to ‘chronic obstructive pulmonary disease’ (COPD) has minimally changed in recent decades while ‘the incidence of bronchiectasis’ is on the rise. The current focus on producing guidelines for these two airway ‘diseases’ h...

Respiratory syncytial virus (RSV) causes annual epidemics of infections affecting the whole population. In vitro, it has been shown to infect and persist in human dendritic cells (DCs) for prolonged periods. Initially persistence is associated with low levels of replication before the virus becomes dormant. Reactivation of viral replication can be...

This manuscript is aimed at encouraging those interested in biofilms and their effects on microbial communities to view the study of chronic airways disease as one of the most challenging and potentially rewarding areas to focus on. To do this it is necessary to review how we have reached 2023 having made so little progress. It is more than two hun...

Respiratory syncytial virus (RSV) causes annual epidemics of acute respiratory disease in large part because antibody levels fall rapidly after infection. RSV is able to infect cultured dendritic cells (DCs) and persist in these cells. Given the importance of DCs in antigen presentation, RSV infection and persistence is likely to be an evolutionary...

Aim: With progressive impairment of lung function, deposition of inhaled drug in the lungs becomes progressively more central, limiting its effectiveness. This pilot study explored the possibility that long slow inhalations might improve delivery of aerosol to the lung periphery in cystic fibrosis patients with moderate lung disease. Methods: Fi...

Many thousands of articles relating to asthma appear in medical and scientific journals each year, yet there is still no consensus as to how the condition should be defined. Some argue that the condition does not exist as an entity and that the term should be discarded. The key feature that distinguishes it from other respiratory diseases is that a...

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching pattern...

Children with asthma face serious mental health risk, but the pathways remain unclear. This study aimed to examine bullying victimisation and perpetration in children with asthma and a comparison sample without a chronic health condition, and the role of bullying in moderating psychosocial adjustment outcomes for those with asthma. A sample of chil...

Bronchoalveolar lavage (BAL) is widely regarded as providing 'gold standard' samples for infective lower respiratory tract disease. Current approaches have been adopted empirically without robust assessment and hence carry many assumptions that have not been tested. Many of these uncertainties were highlighted in the ATS pediatric bronchoscopy guid...

The diagnosis and management of infants and children with a significant viral lower respiratory tract illness remains the subject of much debate and little progress. Over the decades various terms for such illnesses have been in and fallen out of fashion or have evolved to mean different things to different clinicians. Terms such as “bronchiolitis,...

The defining feature of asthma is loss of normal post-natal homeostatic control of airways smooth muscle (ASM). This is the key feature that distinguishes asthma from all other forms of respiratory disease. Failure to focus on impaired ASM homeostasis largely explains our failure to find a cure and contributes to the widespread excessive morbidity...

Rationale: RSV bronchiolitis causes significant infant mortality. Bronchiolitis is characterised by airway epithelial cell (AEC) death, however the mode of death remains unknown. Objectives: To determine whether necroptosis contributes to RSV bronchiolitis pathogenesis via high mobility group box 1 (HMGB1) release. Methods: Nasopharyngeal samp...

Tracheomalacia (TM) and tracheobronchomalacia (TBM) may be primary abnormalities of the large airways or associated with a wide variety of congenital and acquired conditions. The evidence on diagnosis, classification and management is scant. There is no universally accepted classification of severity. Clinical presentation includes early-onset stri...

Introduction Chronic cough in childhood is common and causes much parental anxiety. Eliciting a diagnosis can be difficult as it is a non-specific symptom indicating airways inflammation and this may be due to a variety of aetiologies. A key part of assessment is obtaining an accurate cough history. It has previously been shown that parental report...

Prostaglandin D2 (PGD2) signals through PGD2 receptor 2 (DP2, also known as CRTH2) on type 2 effector cells to promote asthma pathogenesis; however, little is known about its role during respiratory syncytial virus (RSV) bronchiolitis, a major risk factor for asthma development. We show that RSV infection up-regulated hematopoietic prostaglandin D...

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy of electronic monitors, reminder devices or both, on adherence with regular inhaled medication regimes in people with asthma.

It is now more than 200 hundred years since René Laennec invented the stethoscope [1–6], a device that became the unofficial badge of office for doctors for the best part of two centuries. Hailed as one of the great additions to the physician’s non-invasive diagnostic armamentarium, there is no doubt that it has had a huge impact on clinical practi...

In this article, the group chairs of the Paediatric Assembly of the European Respiratory Society (ERS) highlight some of the most interesting findings presented at the 2017 ERS International Congress, which was held in Milan, Italy.

There are many and varied devices currently approved for the administration of inhaled treatments for use in different parts of the world. Well-developed national and local guidelines and training programs for health professionals are important in ensuring that patients are prescribed the best available devices and formulations for their age and di...

This book offers up-to-date information on the recording and analysis of respiratory sounds that will assist in clinical routine. The opening sections deliver basic knowledge on aspects such as the physics of sound and sound transmission in the body, a clear understanding of which is key to good clinical practice. Current techniques of breath sound...

Introduction Persistent bacterial bronchitis (PBB) is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of PBB. Blind, protected brushings were obtained from 20 healthy controls and...

Number of samples sequenced, including controls and repeats. (DOCX)

Demographics of mothers sampled. (DOCX)

Comparison of community alpha diversity measures between blind and non-blind brushes from PBB patients. Using a Wilcoxon paired sign rank test no significant difference was observed between sampling methods. Richness; Z = 1.843, P = 0.068, Shannon-Weiner; Z = -0.017, P = 1, Simpsons; Z = 0.261, P = 0.812, evenness; Z = -0.052, P = 0.973. (TIF)

Differences in bacterial diversity between PBB patients and healthy controls. Using a Wilcoxon sign rank test significant differences in richness (W = 90.5, P = 0.001), Shannon-Weiner (W = 70, P < 0.001), Simpson’s reciprocal (W = 76, P < 0.001) and evenness (W = 65, P < 0.001) were observed between the two groups. (TIF)

Volcano plot indicating the OTUs significantly increased in PBB patients (P < 0.001). Grey points indicate OTUs with P > 0.001. Colours indicate OTU genus, while size indicates the sum of the reads in each OTU. Significant OTUs showed a more than 2.5 fold increase in abundance compared to controls. (TIF)

Ordered bar chart of the top 20 OTUs present in PBB patients with and without a diagnosis of wheeze. Samples are ordered by a Bray Curtis dissimilarity hierarchical cluster upper plot with the lower plot indicating if patient has a diagnosis of wheeze. Key to colours used for each genus is included. (TIF)

NMDS based of Bray-Curtis dissimilarity of the bacterial communities, rarefied to 1154 reads, recovered from both throat and nose swabs of participant mothers. Nose swabs are indicated in blue, throat swabs are indicated in red. Mothers of PBB patients are indicated by triangles while the mothers of controls are shown by circles. (TIF)

Ordered bar chart of the top 20 OTUs present in both paired throat and nose swabs from mothers. Rarefaction resulted in the removal of some samples due to low sequence numbers, the paired samples from these patients were removed to allow paired analysis. Samples are ordered by a Bray Curtis dissimilarity hierarchical cluster. Key to colours used fo...

Supplementary information. This file includes supplementary methods and tables. (DOCX)

Respiratory syncytial virus–bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after...

Correction: After publication of this work [1] it was noticed that the author name Rachael L. DiSantostefano was not spelt correctly as there was a space in her surname between 'Di' and 'Santostefano'. The publisher apologises for this error.

Inhalation of aerosolised medications are the mainstay of treatment for a number of chronic lung diseases and have several advantages over systemically-administered medications. These include more rapid onset of action for drugs such as β-adrenergic agonists when compared with oral medication, high luminal doses for inhaled antibiotics when used to...

Persistent bacterial bronchitis is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of persistent bacterial bronchitis. Blind, protected brushings were obtained from 20 healthy cont...

This European Respiratory Society statement provides a comprehensive overview on protracted bacterial bronchitis (PBB) in children. A task force of experts, consisting of clinicians from Europe and Australia who manage children with PBB determined the overall scope of this statement through consensus. Systematic reviews addressing key questions wer...

Background Human respiratory syncytial virus (RSV) remains the most common cause of severe lower respiratory tract disease amongst infants, and continues to cause annual epidemics of respiratory disease every winter worldwide. Demonstrating placental transmission of viable RSV in human samples is a major paradigm shift in respiratory routes conside...

The upper gastrointestinal tract and the airways are closely related both anatomically and embryologically. It is therefore not surprising that an abnormality of the normal process of dealing with ingested food substances and liquids may impact on the lungs. For certain conditions such as neurological disorders leading to impaired co-ordination of...

Severe viral lower respiratory infections are a major cause of infant morbidity. In developing countries, respiratory syncytial virus (RSV)-bronchiolitis induces significant mortality, whereas in developed nations the disease represents a major risk factor for subsequent asthma. Susceptibility to severe RSV-bronchiolitis is governed by gene–environ...

The recent recognition that the conducting airways are not “sterile” and that they have their own dynamic microbiome, together with the rapid advances in our understanding of microbial biofilms and their roles in the causation of respiratory diseases (such as chronic bronchitis, sinusitis, and chronic otitis media), permit us to update the “vicious...

Background Inhaled corticosteroids (ICS) are the primary treatment for persistent asthma. Currently available ICS have differing particle size due to both formulation and propellant, and it has been postulated that this may impact patient outcomes. This structured literature review and meta-analysis compared the effect of small and standard particl...

In this article, the Group Chairs of the Paediatric Assembly of the European Respiratory Society (ERS) highlight some of the most interesting abstracts presented at the 2016 ERS International Congress, which was held in London.

Objectives: To identify and synthesise evidence on the diagnostic accuracy of FE NO for asthma in adults. Materials and methods: Systematic searches (nine key biomedical databases and trial registers) were carried out to November 2014. Records were included if they: recruited patients with the symptoms of asthma; used a single set of inclusion c...

Background Suboptimal adherence to inhaled steroids is common in children with asthma and is associated with poor disease control, reduced quality of life and even death. Previous studies using feedback of electronically monitored adherence data have demonstrated improved adherence, but have not demonstrated a significant impact on clinical outcome...

Dysfunctional breathing is a significant cause of morbidity, adversely affecting an individual's quality of life. There is currently no data from paediatric centres on the impact of breathing retraining for dysfunctional breathing. Symptoms and quality of life were measured in 34 subjects referred sequentially for breathing retraining to the first...

Respiratory syncytial virus (RSV) causes annual winter epidemics of respiratory disease effecting the whole population. RSV has an assumed airborne transmission; however recent studies have shown evidence for maternal transmission in mouse models and by detection in cord blood mononucleocytes (CBM). Together with RSV persistence reported in mononuc...

Introduction: Abortive RSV replication occurs in in vitro cell lines and animal models in presence of the monoclonal antibody Palivizumab. Naturally present RSV antibodies are known to wane giving rise to the possibility of reactivation of viral replication. Aims: The study was to determine whether latent RSV might be reactivated in a cell culture...

Some in vitro studies have indicated a possible link between respiratory syncytial virus (RSV) infection and exposure to Nitric Oxide (NO). However, these studies used much higher NO concentrations than normally found in the ambient environment. This preliminary study explored whether an association was present with short-term exposure to NO in the...

Key points Excessive exercise-induced shortness of breath is a common complaint. For some, exercise-induced bronchoconstriction is the primary cause and for a small minority there may be an alternative organic pathology. However for many, the cause will be simply reaching their physiological limit or be due to a functional form of dysfunctional bre...

Background: We sought to identify predictors of asthma development following severe early childhood RSV bronchiolitis. Different definitions of asthma were also compared. Methods: This longitudinal, observational study (N = 343) followed patients (<2 years old) from a placebo-controlled trial (N = 979) of montelukast after RSV bronchiolitis to i...

The Paediatric Assembly of the European Respiratory Society (ERS) maintained its high profile at the 2015 ERS International Congress in Amsterdam. There were symposia on preschool wheeze, respiratory sounds and cystic fibrosis; an educational skills workshop on paediatric respiratory resuscitation; a hot topic session on risk factors and early orig...

Background: The European Respiratory Society (ERS) lung sounds repository contains 20 audiovisual recordings of children and adults. The present study aimed at determining the interobserver variation in the classification of sounds into detailed and broader categories of crackles and wheezes. Methods: Recordings from 10 children and 10 adults we...

Pulmonary infections remain a major cause of infant and child mortality worldwide and are responsible for a substantial burden of morbidity. During the 2015 European Respiratory Society International Congress in Amsterdam, some of the main findings from peer-reviewed articles addressing this topic that were published in the preceding 12 months were...

Background: Primary respiratory syncytial virus (RSV) infections are characterised by high levels of IL-8 and an intense neutrophilia. Little is known about the cytokine responses in secondary infections. Pre-school children experiencing a RSV secondary infections were recruited from the siblings of infants admitted to hospital with RSV acute bron...

The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide (FeNO) measured in a clinical setting for the management of asthma in adults. 13 electronic databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-...

Background Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of eosinophilic inflammation which may be used to guide the management of asthma in childhood. Objectives To synthesise the available evidence on the efficacy of FeNO-guided management of childhood asthma. Methods Databases including MEDLINE and the Cochrane Library were...

Auscultation of the lung remains an essential part of physical examination even though its limitations, particularly with regard to communicating subjective findings, are well recognised. The European Respiratory Society (ERS) Task Force on Respiratory Sounds was established to build a reference collection of audiovisual recordings of lung sounds t...

One of the keys to high quality paediatric asthma management is the provision of age appropriate information regarding the disease and its management. In order to determine whether the generation of a minimum dataset of information which can be translated into a wide range of languages might be used to assist children and their parents around the w...

Background: Acute bronchiolitis is the commonest cause of hospitalisation in infancy. Currently management consists of supportive care and oxygen. A Cochrane review concluded that, "nebulised 3 % saline may significantly reduce the length of hospital stay". We conducted a systematic review of controlled trials of nebulised hypertonic saline (HS) f...

Background: High fractions of exhaled nitric oxide (FeNO) in the breath of patients with symptoms of asthma are correlated with high levels of eosinophils and indicate that a patient is likely to respond to inhaled corticosteroids. This may have a role in the diagnosis and management of asthma. Objective: To assess the diagnostic accuracy, clini...

Background: Respiratory syncytial virus (RSV) causes annual epidemics of respiratory disease that effects the whole population. This observation suggests RSV is able to prevent the induction of effective long term immune responses leading to poor herd immunity. U Studies demonstrating latent RSV in dendritic cells (DC) and a recent rodent study sug...

Background: Respiratory syncytial virus (RSV) has been shown to productively infect dendritic cells (DC), and to have the capacity to remain dormant within these cells for prolonged periods. However, whether RSV persists in a latent form or continues replicating at low levels within the lung between annual epidemics remains unknown. These observati...

Introduction: Adherence to inhaled steroids is often sub-optimal in childhood asthma, with multiple consequences including poor disease control and increased health care utilisation. Aims and Objectives: To investigate whether a complex intervention comprising electronic adherence monitoring with feedback and reminder alarms can improve clinical ou...

Acute bronchiolitis is the most common cause of hospitalisation in infancy. Supportive care and oxygen are the cornerstones of management. A Cochrane review concluded that the use of nebulised 3% hypertonic saline (HS) may significantly reduce the duration of hospitalisation. To test the hypothesis that HS reduces the time to when infants were asse...

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the efficacy of electronic monitors, reminder devices or both, on adherence with regular inhaled medication regimes in people with asthma.

Aim Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine...

Background The ERS Task Force on lung sounds was set up in 2012 to establish a repository of audiovisual recordings of lung auscultation for the standardization of nomenclature. We report agreement among the six members of the Task Force on the first 16 recordings. Methods Various adventitious sounds in recordings of lung sounds of 15 seconds durat...

Background: The Easyhaler(®) (EH) device-metered dry powder inhaler containing budesonide and formoterol is being developed for asthma and chronic obstructive pulmonary disease (COPD). As a part of product optimization, a series of in vitro and in vivo studies on flow rate dependency were carried out. Methods: Inspiratory flow parameters via EH...

Adherence to inhaled steroids is suboptimal in many children with asthma and can lead to poor disease control. Many previous studies in paediatric populations have used subjective and inaccurate adherence measurements, reducing their validity. Adherence studies now often use objective electronic monitoring, which can give us an accurate indication...

We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study...

Historically, thoracic kyphosis has been reported to be common amongst patients with cystic fibrosis (CF). The mechanisms leading to the development of this abnormality of the chest wall are not fully understood. In order to explore the prevalence of the condition amongst children with CF in the early twenty-first century and to explore factors tha...

Background: Dysfunctional breathing is described as chronic or recurrent changes in breathing pattern causing respiratory and non-respiratory symptoms. It is an umbrella term that encompasses hyperventilation syndrome and vocal cord dysfunction. Dysfunctional breathing affects 10% of the general population. Symptoms include dyspnoea, chest tightne...

The rate of technological improvement continues to accelerate. Regulators in every field dealing with consumer products continue to set ever higher standards to protect consumers from adverse events and use 'recalls' to remove products that prove to be harmful from the market. In the field of medical products in general the issues of 'human factors...

Chronic cough is common in the paediatric population, yet the true prevalence of this condition remains difficult to define. Protracted bacterial bronchitis (PBB) is a disease caused by the chronic infection of the conducting airways. In many children the condition appears to be secondary to impaired mucociliary clearance that creates a niche for b...

Background: Protracted bacterial bronchitis is a major cause of persistent cough in childhood. The organisms most commonly isolated are nontypable Haemophilus influenzae and Streptococcus pneumoniae . There are no studies addressing typing of these organisms when recovered from the lower airways. Methods: Isolates of these two organisms (identif...

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and imple...

Respiratory Syncytial Virus (RSV) causes annual epidemics of respiratory disease particularly affecting infants. The associated airway inflammation is characterized by an intense neutrophilia. This neutrophilic inflammation appears to be responsible for much of the pathology and symptoms. Previous work from our group had shown that there are factor...

Aspiration syndromes facilitate the colonization of the lower airways with bacterial pathogens and predispose to recurrent chest infections, chronic suppurative lung disease and bronchiectasis. In recent years important steps forward have been made in the understanding of the physiology of swallowing, the mechanisms underlying gastro-oesophageal re...

A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of ae...

The 1000 Years of Pharmaceutical Aerosols Conference convened posing the question; "what remains to be done?" When applying this question to the topic of inhaler devices, two hugely different perspectives could be taken. On the one hand, it could be argued that because there is an array of delivery systems available and the industry, prescribing ph...

Introduction and Objectives RSV causes winter epidemics of respiratory disease. Active infection is virtually absent in summer months. Infected ciliated airway epithelial cells, local macrophages and dendritic cells secrete cytokines including interleukins (IL) 6 and 8, promoting a strong neutrophilic response that is important in disease clearance...

Introduction and Objectives RSV causes winter epidemics of respiratory disease particularly in infants and the immunocompromised. Infected ciliated airway epithelial cells, local macrophages and dendritic cells secrete cytokines including interleukins (IL) 6 and 8, promoting a strong neutrophilic response that is important in disease clearance and...

Current diagnostic labelling of childhood bronchiectasis by radiology has substantial limitations. These include the requirement for two high resolution computerised tomography [HRCT] scans (with associated adversity of radiation) if criteria is adhered to, adoption of radiological criteria for children from adult data, relatively high occurrence o...

OBJECTIVE: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab. METHODS: This randomized, double-blind, multinati...

The respiratory syncytial virus should be considered as the most likely pathogen in an infant or young child with a significant acute lower respiratory tract infection during the characteristic epidemic season. While the diagnosis of an RSV infection is relatively straight forward, the clinical diagnosis applied to the associate illness is far less...