Impaired Mucociliary Clearance Research Articles

Rethinking bronchiectasis as an inflammatory disease.

Bronchiectasis is understood to be the result of a complex interaction between infection, impaired mucociliary clearance, inflammation, and lung damage. Current therapeutic approaches to bronchiectasis are heavily focused on management of infection along with enhancing mucus clearance. Long-term antibiotics have had limited success in clinical trials, suggesting a need to re-evaluate the concept of bronchiectasis as an infective disorder. We invoke the example of asthma, for which treatment paradigms shifted away from targeting smooth muscle constriction, towards permanently suppressing airway inflammation, reducing risk and ultimately inducing remission with precision anti-inflammatory treatments. In this Review, we argue that bronchiectasis is primarily a chronic inflammatory disease, requiring early identification of at-risk individuals, and we introduce a novel concept of disease activity with important implications for clinical practice and future research. A new generation of novel anti-inflammatory treatments are under development and repurposing of anti-inflammatory agents from other diseases could revolutionise patient care.

Biomarkers in bronchiectasis.

Bronchiectasis is a heterogeneous disease with multiple aetiologies and diverse clinical features. There is a general consensus that optimal treatment requires precision medicine approaches focused on specific treatable disease characteristics, known as treatable traits. Identifying subtypes of conditions with distinct underlying biology (endotypes) depends on the identification of biomarkers that are associated with disease features, prognosis or treatment response and which can be applied in clinical practice. Bronchiectasis is a disease characterised by inflammation, infection, structural lung damage and impaired mucociliary clearance. Increasingly there are available methods to measure each of these components of the disease, revealing heterogeneous inflammatory profiles, microbiota, radiology and mucus and epithelial biology in patients with bronchiectasis. Using emerging biomarkers and omics technologies to guide treatment in bronchiectasis is a promising field of research. Here we review the most recent data on biomarkers in bronchiectasis.

Regional anesthesia in a patient with primary ciliary dyskinesia: A case report

BACKGROUND Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases, otolaryngological diseases, central nervous system abnormalities, reproductive system abnormalities, and cardiac function abnormalities. General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease. CASE SUMMARY A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture. Three years prior, he had been diagnosed with PCD. At that time, he had experienced several episodes of pneumonia, sinusitis, and chronic middle ear infections, for which he underwent surgical interventions. At the current admission, he presented with cough and sputum but no other respiratory symptoms. A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe. For the surgical procedure and postoperative pain management, combined spinal-epidural anesthesia was employed. The patient’s postoperative pain score was measured by the numerical rating scale (NRS). On the day of surgery, his NRS was 5 points. By the second postoperative day, the NRS score had decreased to 2–3 points. The epidural catheter was removed on the fourth day following the operation. The patient was subsequently discharged no respiratory complications. CONCLUSION We performed combined spinal-epidural anesthesia in a patient with PCD. The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.

IJCM_83A: Primary Ciliary Dyskinesia in a child

Background: PCD is rare genetic disorder with incidence of 1:10,000. We present a 10-year-boy who came with recurrent respiratory-infections with Dextrocardia and bilateral Bronchiectasis for interesting clinical presentation. Objective: PCD is rare inherited disease with mutations which impair normal cilia function, characterized by impaired muco-ciliary clearance, causing recurrent-respiratory infections leading to bronchiectasis. Treatment includes preventing and managing complications. Methodology: 10-year-old child came cough-cold since 2 days, and hurried breathing since 1 day. Child had multiple episodes of respiratory- infections which was treated with antibiotics and nebulization on OP basis. Developmental delay also noted, currently in speech domain, can speak 2-3 words. On examination, open mouth breathing and clubbing(grade 3) present. On auscultation bilateral bronchial breath sounds with coarse crepitations. Heart sounds heard louder on right side, but no murmur was heard. Chest X-ray and 2D-ECHO showed Situs-Solitus with Dextrocardia. Child required non-invasive ventilation and IV antibiotics for treatment. Child was weaned off to room air by day 4. CT Thorax done showed bronchiectatic changes in bilateral lung with volume loss of right hemithorax with mediastinal shift to right. CT Nasopharynx and OMC done for open-mouth breathing was normal, and advised steroid nasal spray for nasal blockage. Physiotherapist counselled parents about postural drainage. Genetic testing for PCD was sent, report awaited. He is on regular follow up and doing well. Results: Primary defect in PCD is structure and/or function of cilia leading to accumulation of secretions. Diagnostic criteria includes recurrent chest infections, bronchitis, and rhinitis, with situs-inversus, infertility, decreased mucociliary clearance and cilia showing ultrastructural defect on electron microscopy. We suspected PCD with clinical features and imaging studies. Conclusion: Patients are frequently troubled by repeated infections for which they need to seek medical attention which is reason for morbidity. As there is no specific treatment, early diagnosis and prevention of complication is key to management.

Bronchial Asthma and Mucociliary Clearance - A Bidirectional Relationship

Abstract: The integrity of the airway epithelium plays an important role in the defence against pathogens and various immunogenic stimuli from the external environment. Properly functioning mucociliary clearance is an indispensable part of the respiratory system defence and it relies on adequate viscoelastic properties of mucus, as well as the intact function of a significant number of healthy ciliated cells. The movement of the cilia can be affected by many endogenous and exogenous factors. Complex mucociliary clearance dysfunction can be seen as a part of the respiratory system inflammation. Bronchial asthma is one of the most common inflammatory diseases of the respiratory system. It is characterised by structural and functional changes in the airways. The last decades of bronchial asthma research point to asthmatic inflammation as the cause of airway remodelling with subsequent impairment of mucociliary transport function. Changes in the respiratory epithelium in patients with bronchial asthma include hypertrophy of secretory cells, overproduction of mucus, increase in mucus viscosity, decline of ciliated cells, decrease of ciliary beat frequency, and more. Cytokines of T2-high type of asthmatic inflammation, such as interleukin IL-13 and IL-4, have been shown to contribute to these changes in the airway epithelium significantly. There is strong evidence of cytokine-induced overexpression of important transcription factors, which results in hyper- and metaplasia of secretory cells and also transdifferentiation of ciliary cells. Impaired mucociliary clearance increases the risk of airway infection and contributes to the worsening of bronchial asthma control.

Chronic Rhinosinusitis-Microbiological Etiology, Potential Genetic Markers, and Diagnosis.

Chronic rhinosinusitis (CRS) is a significant public health problem. Bacterial colonization and impaired mucociliary clearance play a significant role in the inflammatory process. Several inflammatory pathways and host defense elements are altered in CRS, which may contribute to observed differences in the microbiome. To date, researching CRS has been difficult due to limited access to the studied tissue and a lack of available biomarkers. Ongoing scientific research is increasingly based on simple and objective analytical methods, including sensors, detection with PCR, and sequencing. Future research on microbiota and human factors should also include genomics, transcriptomics, and metabolomics approaches. This report analyzes the changes that occur in the paranasal sinuses of people with acute and chronic rhinosinusitis, the composition of the microbiota, the human genetic markers that may shed light on the predisposition to CRS, and the advantages and disadvantages of classical and molecular diagnostic methods, as well as addressing the difficulties of sinusitis treatment.

The primary ciliary dyskinesia-related genetic risk score is associated with susceptibility to adult-onset asthma.

Disturbance of mucociliary clearance is an important factor in the pathogenesis of asthma. We hypothesized that common variants in genes responsible for ciliary function may contribute to the development of asthma with certain phenotypes. Three independent adult Japanese populations (including a total of 1,158 patients with asthma and 2,203 non-asthmatic healthy participants) were studied. First, based on the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/), we selected 12 common single-nucleotide polymorphisms (SNPs) with molecular consequences (missense, nonsense, and 3'-untranslated region mutation) in 5 primary ciliary dyskinesia (PCD)-related genes and calculated a PCD-genetic risk score (GRS) as a cumulative effect of these PCD-related genes. Second, we performed a two-step cluster analysis using 3 variables, including PCD-GRS, forced expiratory volume in 1 second (%predicted FEV1), and age of asthma onset. Compared to adult asthma clusters with an average PCD-GRS, clusters with high and low PCD-GRS had similar overall characteristics: adult-onset, female predominance, preserved lung function, and fewer features of type 2 immunity as determined by IgE reactivity and blood eosinophil counts. The allele frequency of rs1530496, a SNP representing an expression quantitative trait locus (eQTL) of DNAH5 in the lung, showed the largest statistically significant difference between the PCD-GRS-High and PCD-GRS-Low asthma clusters (p = 1.4 x 10-15). Genes associated with PCD, particularly the common SNPs associated with abnormal expression of DNAH5, may have a certain influence on the development of adult-onset asthma, perhaps through impaired mucociliary clearance.

Updated epithelial barrier dysfunction in chronic rhinosinusitis: Targeting pathophysiology and treatment response of tight junctions.

Tight junction (TJ) proteins establish a physical barrier between epithelial cells, playing a crucial role in maintaining tissue homeostasis by safeguarding host tissues against pathogens, allergens, antigens, irritants, etc. Recently, an increasing number of studies have demonstrated that abnormal expression of TJs plays an essential role in the development and progression of inflammatory airway diseases, including chronic obstructive pulmonary disease, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS) with or without nasal polyps. Among them, CRS with nasal polyps is a prevalent chronic inflammatory disease that affects the nasal cavity and paranasal sinuses, leading to a poor prognosis and significantly impacting patients' quality of life. Its pathogenesis primarily involves dysfunction of the nasal epithelial barrier, impaired mucociliary clearance, disordered immune response, and excessive tissue remodeling. Numerous studies have elucidated the pivotal role of TJs in both the pathogenesis and response to traditional therapies in CRS. We therefore to review and discuss potential factors contributing to impair and repair of TJs in the nasal epithelium based on their structure, function, and formation process.

Redox Imbalance in Nasal Epithelial Cells of Primary Ciliary Dyskinesia Patients.

Background: Primary Ciliary Dyskinesia (PCD) represents a rare condition marked by an abnormal mobility pattern of cilia and flagella, resulting in impaired mucociliary clearance. This deficiency leads to recurrent infections and persistent inflammation of the airways. While previous studies have indicated heightened oxidative stress levels in the exhaled breath condensate of pediatric PCD patients, the assessment of oxidative stress within the affected respiratory tissue remains unexplored. Aims: To assess the oxidative status of human nasal epithelial cells (NECs) in PCD patients. Methods: Thirty-five PCD patients and thirty-five healthy control subjects were prospectively included in the study. Levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), intracellular Ca2+, plasma membrane potential, and oxidative damage in lipids and proteins were measured. In addition, apoptosis and mitochondrial function were analyzed by flow cytometry in NECs. Results: NECs from PCD patients showed reduced levels of apoptosis (p = 0.004), superoxide anion (O2-, p = 0.018), peroxynitrite (ONOO-, p = 0.007), nitric oxide (NO, p = 0.007), mitochondrial hydrogen peroxide (mtH2O2, p < 0.0001), and mitochondrial superoxide anion (mtO2-, p = 0.0004) and increased mitochondrial mass (p = 0.009) compared to those from healthy individuals. No significant differences were observed in oxidized proteins (p = 0.137) and the oxidized/reduced lipid ratio (p = 0.7973). The oxidative profile of NEC cells in PCD patients, according to their ciliary motility, recurrent otitis, recurrent pneumonia, atelectasis, bronchiectasis, and situs inversus, showed no statistically significant differences in the parameters studied. Conversely, patients with chronic rhinosinusitis exhibited lower levels of ONOO- than PCD patients without this condition, with no significant differences related to other symptoms. Conclusions: Our findings strongly suggest the presence of a redox imbalance, specifically leaning toward a reductive state, in PCD patients.

RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis

A core pathophysiologic feature underlying many respiratory diseases is multiciliated cell dysfunction, leading to inadequate mucociliary clearance. Due to the prevalence and highly variable etiology of mucociliary dysfunction in respiratory diseases, it is critical to understand the mechanisms controlling multiciliogenesis that may be targeted to restore functional mucociliary clearance. Multicilin, in a complex with E2F4, is necessary and sufficient to drive multiciliogenesis in airway epithelia, however this does not apply to all cell types, nor does it occur evenly across all cells in the same cell population. In this study we further investigated how co-factors regulate the ability of Multicilin to drive multiciliogenesis. Combining data in mouse embryonic fibroblasts and human bronchial epithelial cells, we identify RBL2 as a repressor of the transcriptional activity of Multicilin. Knockdown of RBL2 in submerged cultures or phosphorylation of RBL2 in response to apical air exposure, in the presence of Multicilin, allows multiciliogenesis to progress. These data demonstrate a dynamic interaction between RBL2 and Multicilin that regulates the capacity of cells to differentiate and multiciliate. Identification of this mechanism has important implications for facilitating MCC differentiation in diseases with impaired mucociliary clearance.

Specialized proresolving mediator resolvin E1 corrects the altered cystic fibrosis nasal epithelium cilia beating dynamics

In cystic fibrosis (CF), impaired mucociliary clearance leads to chronic infection and inflammation. However, cilia beating features in a CF altered environment, consisting of dehydrated airway surface liquid layer and abnormal mucus, have not been fully characterized. Furthermore, acute inflammation is normally followed by an active resolution phase requiring specialized proresolving lipid mediators (SPMs) and allowing return to homeostasis. However, altered SPMs biosynthesis has been reported in CF. Here, we explored cilia beating dynamics in CF airways primary cultures and its response to the SPMs, resolvin E1 (RvE1) and lipoxin B4 (LXB4). Human nasal epithelial cells (hNECs) from CF and non-CF donors were grown at air-liquid interface. The ciliary beat frequency, synchronization, orientation, and density were analyzed from high-speed video microscopy using a multiscale Differential Dynamic Microscopy algorithm and an in-house developed method. Mucins and ASL layer height were studied by qRT-PCR and confocal microscopy. Principal component analysis showed that CF and non-CF hNEC had distinct cilia beating phenotypes, which was mostly explained by differences in cilia beat organization rather than frequency. Exposure to RvE1 (10 nM) and to LXB4 (10 nM) restored a non-CF-like cilia beating phenotype. Furthermore, RvE1 increased the airway surface liquid (ASL) layer height and reduced the mucin MUC5AC thickness. The calcium-activated chloride channel, TMEM16A, was involved in the RvE1 effect on cilia beating, hydration, and mucus. Altogether, our results provide evidence for defective cilia beating in CF airway epithelium and a role of RvE1 and LXB4 to restore the main epithelial functions involved in the mucociliary clearance.

Magnetic Resonance Imaging of Pulmonary and Paranasal Sinus Abnormalities in Children with Primary Ciliary Dyskinesia Compared to Children with Cystic Fibrosis.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are characterized by inherited impaired mucociliary clearance leading to chronic progressive lung disease as well as chronic rhinosinusitis (CRS). The diseases share morphological and functional commonalities on magnetic resonance imaging (MRI) of the lungs and paranasal sinuses, but comparative MRI studies are lacking. Objectives: To determine whether PCD shows different associations of pulmonary and paranasal sinus abnormalities on MRI and lung function test results in children (infants to adolescents) compared with children with CF. Methods: Eighteen children with PCD (median age, 9.5 [IQR, 3.4-12.7] yr; range, 0-18 yr) and 36 age-matched CF transmembrane conductance regulator modulator-naive children with CF (median age, 9.4 [3.4-13.2] yr; range, 0-18 yr) underwent same-session chest and paranasal sinus MRI as well as spirometry (to determine forced expiratory volume in 1 s percent predicted) and multiple-breath washout (to determine lung clearance index z-score). Pulmonary and paranasal sinus abnormalities were assessed using previously validated chest MRI and CRS-MRI scoring systems. Results: Mean chest MRI global score was similar in children with PCD and CF (15.0 [13.5-20.8] vs. 15.0 [9.0-15.0]; P = 0.601). Consolidations were more prevalent and severe in children with PCD (56% vs. 25% and 1.0 [0.0-2.8] vs. 0.0 [0.0-0.3], respectively; P < 0.05). The chest MRI global score correlated moderately with forced expiratory volume in 1 second percent predicted in children with PCD and children with CF (r = -0.523 and -0.687; P < 0.01) and with lung clearance index in children with CF (r = 0.650; P < 0.001) but not in PCD (r = 0.353; P = 0.196). CRS-MRI sum score and mucopyocele subscore were lower in children with PCD than in children with CF (27.5 [26.3-32.0] vs. 37.0 [37.8-40.0] and 2.0 [0.0-2.0] vs. 7.5 [4.8-9.0], respectively; P < 0.01). CRS-MRI sum score did not correlate with chest MRI score in PCD (r = 0.075-0.157; P = 0.557-0.788) but correlated moderately with MRI morphology score in CF (r = 0.437; P < 0.01). Conclusions: MRI detects differences in lung and paranasal sinus abnormalities between children with PCD and those with CF. Lung disease does not correlate with CRS in PCD but correlates in CF.

Histopathology of Recalcitrant Maxillary Sinusitis Necessitating Endoscopic Medial Maxillectomy.

Endoscopic medial maxillectomy (EMM) is an effective intervention for patients with recalcitrant maxillary sinusitis after previous middle meatal antrostomy. The pathophysiology of refractory maxillary sinusitis is incompletely understood. We aim to identify trends in structured histopathology (SHP) to better understand how tissue architecture changes contribute to refractory sinusitis and impaired mucociliary clearance. All patients who underwent EMM or standard maxillary antrostomy for recalcitrant maxillary sinusitis of various forms were included. Retrospective chart review was conducted to collect information on demographics, disease characteristics, comorbid conditions, culture data, and SHP reports. Chi-squared and logistic regression analyses were performed for SHP variables. Forty-one patients who underwent EMM and 464 patients who underwent maxillary antrostomy were included. On average, the EMM cohort was 10 years older (60.9 years vs. 51.1 years; p = 0.001) and more often had a history of prior sinus procedures (73.2% vs. 40.9%; p < 0.001). EMM patients had higher rates of fibrosis (34.1% vs. 15.1%, p = 0.002), and this remained statistically significant when controlling for prior sinus procedures and nasal polyposis (p = 0.001). Cultures positive for pseudomonas aeruginosa (38.2% vs. 5.6%, p < 0.001) and coagulase negative staphylococcus (47.1% vs. 23.5%, p = 0.003) were more prevalent in the EMM group. Fibrosis and bacterial infections with Pseudomonas and coagulase negative Staphylococcus were more prevalent in patients requiring EMM. This may contribute to the multifactorial etiology of impaired mucociliary clearance in patients with recalcitrant maxillary sinusitis. 3 Laryngoscope, 134:2646-2652, 2024.

Primary Ciliary Dyskinesia

Primary ciliary dyskinesia, also known as immotile-ciliary syndrome causes impaired mucociliary clearance most notably in the upper and lower airways. We describe a middle aged man with a history of primary ciliary dyskinesia who presented to the hospital following a witnessed seizure at home.

Saliva as a Non Invasive Specimen for Section Assessment of Chronic Obstructive Pulmonary Disease: A Cross-sectional Study

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Impaired mucociliary clearance due to altered respiratory physiology in COPD presents an exceptional opportunity for bacterial proliferation. Sampling the respiratory tract using sputum or Bronchoalveolar Lavage (BAL) can be labourious and inconvenient, particularly in chronically debilitated patients. Saliva offers an interesting and non invasive method for assessing COPD patients and preventing exacerbations. Aim: To use saliva to analyse the association between the frequency of positive Potentially Pathological Bacterial Isolates (PPBI) and COPD exacerbations in relation to the frequency of exacerbations and the severity of the disease. Materials and Methods: This cross-sectional study was conducted over a period of one year (July 2022 to June 2023) among COPD patients attending the outpatient department at the Department of Respiratory Medicine, GMERS Medical College, Gotri, Vadodara, Gujarat, India. A total of 60 patients with COPD, diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021 guidelines, were included. The patients were categorised based on the severity of airflow limitation, GOLD “ABCD” assessment tool, and number of exacerbations. Salivary samples were collected and subjected to microbiological analysis using laboratory conventional culture techniques. Analysis of Variance (ANOVA) and t-tests were applied. Results: The mean age was 64±5.1 years. S. pneumoniae and H. influenza were common bacterial findings in all stages of COPD, while E. coli and A. baumannii were isolated in GOLD Group D patients. Disease severity also showed a significant association with oral bacterial composition (p=0.010) and the frequency of exacerbations (p=0.03). Conclusion: The current study demonstrates an association between oral bacteria and COPD, especially in patients with severe symptoms (GOLD Group D). Additionally, patients with repeated exacerbations exhibited a different oral bacterial composition, thus supporting the use of saliva as a non invasive specimen for assessing heterogeneous diseases like COPD and designing an empiric antibiotic regimen for those PPBI.

Pathogenesis of Achromobacter xylosoxidans respiratory infections: colonization, persistence, and transcriptome profiling in synthetic cystic fibrosis sputum medium

ABSTRACT Cystic fibrosis (CF) is a genetic disease affecting epithelial ion transport, resulting in thickened mucus and impaired mucociliary clearance. Persons with CF (pwCF) experience life-long infections of the respiratory mucosa caused by a diverse array of opportunists, which are leading causes of morbidity and mortality. In recent years, there has been increased appreciation for the range and diversity of microbes causing CF-related respiratory infections. The introduction of new therapeutics and improved detection methodology has revealed CF-related opportunists such as Achromobacter xylosoxidans ( Ax ). Ax is a Gram-negative bacterial species which is widely distributed in environmental sources and has been increasingly observed in sputa and other samples from pwCF, typically in patients in later stages of CF disease. In this study, we characterized CF clinical isolates of Ax and tested colonization and persistence of Ax in respiratory infection using immortalized human CF respiratory epithelial cells and BALB/c mice. Genomic analyses of clinical Ax isolates showed homologs for factors including flagellar synthesis, antibiotic resistance, and toxin secretion systems. Ax isolates adhered to polarized cultures of CFBE41o- human immortalized CF bronchial epithelial cells and caused significant cytotoxicity and depolarization of cell layers. Ax colonized and persisted in mouse lungs for up to 72 h post infection, with inflammatory consequences that include increased neutrophil influx in the lung, lung damage, cytokine production, and mortality. We also identified genes that are differentially expressed in synthetic CF sputum media. Based on these results, we conclude that Ax is an opportunistic pathogen of significance in CF.

Features of combined mucoactive therapy for bronchopulmonary diseases in children in outpatient practice

In 2022, ARVI rates among the paediatric population were 72281.8 per 100,000, which is 6.2% higher than such rates in 2021 (68062.5 per 100,000; p &lt; 0.05). Estimated influenza rates among the paediatric population were 165.8 per 100,000, which is 2.9 times higher than this rate in 2021. Impaired mucociliary clearance makes a significant contribution to the pathogenesis of acute and chronic bronchopulmonary diseases. Slowing of mucociliary clearance that results from chronic mucus hyperproduction leads to airway obstruction and infection, which acts as a cause of aggravation of the disease. There’s no question, the choice of a drug that can affect the secretory function of the mucous membrane or the bronchial mucous itself and its evacuation requires an individual approach to each patient. The article presents a detailed review of modern literature, as well as the authors’ own experience about cough therapy methods, including those used in broncho-obstructive syndrome. At the same time, the use of combination drugs that have a simultaneous effect on various pathogenetic mechanisms of respiratory diseases are justified more than ever before. Due to synergistic interactions of its components, the modern combination therapy, including a fixed-dose combination of salbutamol, bromhexine, guaifenesin (Bromhekomb), contributes to the productive treatment of acute bronchopulmonary diseases and exacerbations of chronic bronchopulmonary diseases accompanied by cough, mucostasis and events of mild bronchial obstruction, as well as ensures high compliance, including due to consideration of the syrup dosage form, which is especially important in outpatient paediatric practice

Sleep Respiratory Disorders in Children and Adolescents with Cystic Fibrosis and Primary Ciliary Dyskinesia.

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are genetic respiratory diseases featured by chronic upper and lower airway inflammation and infection, mainly due to impaired mucociliary clearance due to genetic mutations. Sleep is crucial to healthy children's normal physical and psychological development and has an important value in chronic respiratory diseases. Impaired sleep quality, such as sleep deprivation or insufficient sleep during the night, and sleep respiratory disorders (SRDs) are common in 5% to 30% of the general population. Sleep disruption leads to attention deficits, daytime sleepiness, fatigue and mood disorders and correlates to a worsened quality of life. Furthermore, sleep respiratory disorders (SRSs) are under-recognized comorbidities in CF and PCD patients. SRSs include a spectrum of symptoms ranging from primary snoring through upper airway resistance to obstructive sleep apnea (OSA), nocturnal hypoventilation and hypoxemia occurring in people with moderate to severe lung disease and damaging the disease-related outcomes and quality of life. Effective screening during sleep with polysomnography is very important for the timely initiation of efficacious treatments and to prevent worsened respiratory, metabolic and cardiovascular outcomes. However, the impact of SRDs on health and quality of life is still underinvestigated.

BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance.

Airway mucociliary clearance (MCC) is required for host defense and is often diminished in chronic lung diseases. Effective clearance depends upon coordinated actions of the airway epithelium and a mobile mucus layer. Dysregulation of the primary secreted airway mucin proteins, MUC5B and MUC5AC, is associated with a reduction in the rate of MCC; however, how other secreted proteins impact the integrity of the mucus layer and MCC remains unclear. We previously identified the gene Bpifb1/Lplunc1 as a regulator of airway MUC5B protein levels using genetic approaches. Here, we show that BPIFB1 is required for effective MCC in vivo using Bpifb1 knockout (KO) mice. Reduced MCC in Bpifb1 KO mice occurred in the absence of defects in epithelial ion transport or reduced ciliary beat frequency. Loss of BPIFB1 in vivo and in vitro altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC. Finally, we detected colocalization of BPIFB1 and MUC5B in secretory granules in mice and the protein mesh of secreted mucus in human airway epithelia cultures. Collectively, our findings demonstrate that BPIFB1 is an important component of the mucociliary apparatus in mice and a key component of the mucus protein network.NEW & NOTEWORTHY BPIFB1, also known as LPLUNC1, was found to regulate mucociliary clearance (MCC), a key aspect of host defense in the airway. Loss of this protein was also associated with altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC.

Rational mucolytic therapy with ambroxol: controversial and indisputable. A review

Many years of experience in the use of ambroxol is based on its ability to regulate the basic mechanisms of physiological production and transport of bronchial mucus. The main indication for ambroxol is the mucolytic therapy of acute and chronic bronchopulmonary diseases associated with hypersecretion and impaired mucus transport. Ambroxol has a number of the following properties: high secretolytic activity (promotes mucus clearance, facilitates expectoration of sputum, reduces productive cough); anti-inflammatory and antioxidant activity; local analgesic (anesthetic) effect through the blockade of sodium channels of cell membranes. The effect of anesthesia of the mucous membranes is attributed to the new pharmacological action of ambroxol, useful in the treatment of acute respiratory tract infections. The efficacy and safety of ambroxol in clinical practice has been confirmed by half a century of experience in its administration. The purpose of this publication was an up-to-date assessment of the controversial and indisputable chemical, pharmacological, clinical data on the properties of ambroxol in the concept of modern recovery mucolytic therapy that can improve the therapy and prognosis of patients with tracheobronchial secretion hypersecretion, impaired mucociliary clearance and unproductive cough.