The Egyptian Journal of Surgery

Lung cancer is the leading cause of cancer-related mortality worldwide, with the prevalence of the disease continually rising. Therefore, identifying disease-modifying risk factors is critical, with increasing recognition of the impact of sleep quality/sleep disorders. This narrative review summarizes the evidence on the role of five domains of sleep on lung cancer incidence and progression: (i) sleep quality/duration, (ii) sleep disordered breathing, (iii) circadian rhythm disturbances, (iv) sleep-related movement disorders and (v) personal, environmental and social factors that modulate each of these associations. Epidemiological evidence supports reduced sleep duration, increased sleep duration, poor sleep quality, insomnia, obstructive sleep apnea, evening chronotype, peripheral limb movements in sleep, and less robustly for night shift work and restless leg syndrome to be associated with increased risk of lung cancer development, with potential impacts on cancer survival outcomes. Proposed mechanisms underlying the biological plausibility of these epidemiological associations are also explored, with common theories relating to immune dysregulation, metabolic alterations, reductions in melatonin, sympathetic overactivation, increased reactive oxygen species, production of protumorigenic exosomes and inflammation. We also summarized potential treatments addressing impaired sleep quality/sleep disorders and their ability to attenuate the risk of lung cancer and cancer survival. While evidence on reversibility is inconsistent, there are trends toward positive outcomes. Future research should focus on clinical trials to confirm cause and effect relationships, large epidemiologic studies for incidence/prognosis, clarification on the relative efficacy of treatment modalities, and more in vivo animal models to establish the molecular mechanisms underlying these relationships.

During the 2023-2024 season, nirsevimab significantly reduced the risk of bronchiolitis and confirmed RSV infections in primary care, hospital, and pediatric intensive care unit admissions among infants aged 0 to 11 months, even in a season with a high community RSV burden, particularly for older infants. These findings are very useful for public health authorities to continue to implement immunization campaigns against RSV in the coming seasons. Moreover, universal immunization against RSV represents a transformative step towards reducing the burden of RSV in infants. With promising evidence from recent published studies, the expectations for a reduction of RSV-associated hospitalizations, alongside the improvement of public health outcomes and an equitable access to these measures, are high. However, achieving these goals will require addressing challenges related to vaccine uptake, funding, and RSV surveillance to prompt detect resistances due to mutations of the virus. These interventions need to be integrated into public health strategies because they hold the potential to make a significant impact on infant’s health worldwide.

Sleep disorders that involve circadian rhythm disruption and sleep-disordered breathing (SDB) such as obstructive sleep apnea (OSA) are closely linked to respiratory infections. SDB leads to a proinflammatory state due to intermittent hypoxia, sleep fragmentation, increased oxidative stress, and elevation of inflammatory mediators such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and C-reactive protein (CRP). Furthermore, inflammatory mediator levels correlate with SDB severity, especially in people with OSA. Nocturnal microaspiration, gastroesophageal reflux, and associated comorbidities (e.g. obesity) increase the risk of community-acquired pneumonia, viral infections such as SARS-CoV-2, respiratory complications, and death. OSA has been associated with post-COVID syndrome. It also increases the risk of postoperative complications in both adults and children. Circadian rhythm disorders such as insomnia predispose to immune disorders and increase the risk of infection. Chronic conditions such as bronchiectasis, with or without concomitant cystic fibrosis, can lead to structural sleep changes and increase the risk of OSA due to chronic cough, arousals, aspirations, hypoxia, upper airway edema, and overexpression of proinflammatory cytokines. The protective effect of treatment for sleep disorders against respiratory infection is currently unknown. However, in people presenting with respiratory infection, it is important to test for SDB to prevent complications.

AbstractIn this review, we present the efforts made so far in developing effective solutions to prevent infections caused by seven major respiratory pathogens: influenza virus, respiratory syncytial virus (RSV), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Bordetella pertussis, Streptococcus pneumoniae (pneumococcus), Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Advancements driven by the recent coronavirus disease 2019 (COVID-19) crisis have largely focused on viruses, but effective prophylactic solutions for bacterial pathogens are also needed, especially in light of the antimicrobial resistance (AMR) phenomenon. Here, we discuss various innovative key technologies that can help address this critical need, such as (a) the development of Lung-on-Chip ex vivo models to gain a better understanding of the pathogenesis process and the host–microbe interactions; (b) a more thorough investigation of the mechanisms behind mucosal immunity as the first line of defense against pathogens; (c) the identification of correlates of protection (CoPs) which, in conjunction with the Reverse Vaccinology 2.0 approach, can push a more rational and targeted design of vaccines. By focusing on these critical areas, we expect substantial progress in the development of new vaccines against respiratory bacterial pathogens, thereby enhancing global health protection in the framework of the increasingly concerning AMR emergence.

AbstractPulmonary embolism (PE) and obstructive sleep apnea (OSA) remain a major health issue worldwide with potential overlapping pathophysiological mechanisms. PE, the most severe form of venous thromboembolism, is associated with high morbidity and mortality, presenting challenges in management and prevention, especially in high-risk populations. OSA is a prevalent condition characterized by repeated episodes of upper airway closure resulting in intermittent hypoxia and sleep fragmentation. Although the understanding of epidemiological and pathogenic relationships between OSA and PE is still limited, current data suggest that interactions between these two conditions appear to be relevant. OSA is emerging as a novel risk factor for PE, potentially affecting all components of Virchow's triad: hypercoagulability, endothelial dysfunction, and venous stasis. Epidemiological studies indicate a high prevalence of undiagnosed OSA in acute PE patients. Moderate-to-severe OSA has been linked to worse clinical presentations and outcomes. Furthermore, OSA has been associated with increased risks of PE recurrence and mortality. Future research directions should include clarifying the bidirectional relationship between these conditions and evaluating the effectiveness and safety of continuous positive airway pressure therapy in improving outcomes in patients with concurrent acute PE and OSA.

AbstractLower respiratory tract infection (LRTI) is a major cause of neonatal morbidity and mortality worldwide. Maternal vaccination is an effective strategy in protecting young infants from LRTI, particularly in the first few months after birth when infant is most vulnerable, and most primary childhood vaccinations have not been administered. Additionally, maternal vaccination protects the mother from illness during pregnancy and the postnatal period, and the developing fetus from adverse outcomes such as stillbirth and prematurity. In this paper, we review the safety, efficacy, and effectiveness of maternal vaccines against LRTIs, such as pertussis, influenza, coronavirus disease 2019, and respiratory syncytial virus.

AbstractNeuromuscular disorders can cause respiratory impairment by affecting the muscle fibers, neuromuscular junction, or innervation of respiratory muscles, leading to significant morbidity and mortality. Over the past few years, new disease-modifying therapies have been developed and made available for treating different neuromuscular disorders. Some of these therapies have remarkable effectiveness, resulting in the prevention and reduction of respiratory complications. For myasthenia gravis (MG), efgartigimod, ravulizumab, rozanolixizumab, and zilucoplan have been Food and Drug Administration (FDA)-approved for the treatment of acetylcholine receptor (AChR) antibody-positive generalized MG in the past 2 years. Rozanolixiumab is also approved for treating MG caused by muscle-specific tyrosine kinase (MuSK) antibodies. The new MG therapeutics target the complement system or block the neonatal fragment crystallizable (Fc) receptors (FcRn), leading to significant clinical improvement. For spinal muscular atrophy (SMA), nusinersen (intrathecal route) and risdiplam (oral route) modify the splicing of the SMN2 gene, increasing the production of normal survival motor neuron (SMN) protein. Onasemnogene abeparvovec is a gene replacement therapy that encodes a functional SMN protein. All SMA medications, particularly onasemnogene abeparvovec, have led to clinically meaningful improvement. For late-onset Pompe disease (LOPD), avalglucosidase alfa has shown a greater improvement in respiratory function, ambulation, and functional outcomes in comparison to alglucosidase alfa, and cipaglucosidase alfa combined with miglustat has shown improvement in respiratory and motor function in a cohort of enzyme replacement therapy-experienced LOPD patients. Amyotrophic lateral sclerosis (ALS) remains a challenge. The two most recent FDA-approved medications, namely sodium phenylbutyrate and tofersen, may slow down the disease by a few months in a selected population but do not stop the progression of the disease.

AbstractRespiratory infections are associated with a huge burden of disease every year and disproportionately affect older adults, namely those aged 65 years and older. Older adults are at increased risk of infections compared with their younger counterparts, and once infected, have a higher risk of experiencing severe disease course, complications, and long-term sequelae. Therefore, vaccination is clearly a key strategy to prevent infection and its attendant negative consequences. We review here the burden of common respiratory diseases in older adults, namely influenza, pneumococcal disease, and respiratory syncytial virus. We then review some of the challenges facing immunization of older adults, namely immunosenescence, inflammaging, and low vaccine uptake. Next, potential opportunities for overcoming these challenges are reviewed, including the use of higher antigen doses and/or adjuvants in vaccine formulations for older adults, and the potential of multiomics analyses to improve development, performance, and implementation of vaccines.

AbstractAspiration pneumonia is a clinical entity with important ethical considerations. It is imperative for clinicians to understand these considerations to best provide counsel to patients and their families, allowing them to make fully informed decisions. Given that aspiration pneumonia is frequently associated with end of life, there are palliative medicine principles that may help in the treatment of this disease.

AbstractPatients with aspiration pneumonia often develop this lung infection due to poor oral health or because the contents of the digestive tract or upper airway enter the lower airway traversing the larynx through different mechanisms. Prevention of this condition is directed at the mechanism by which it occurs. The elderly are the most likely to suffer from aspiration pneumonia, occasionally due to issues related to poor dental health, but more frequently due to abnormal swallowing, which may appear after a stroke, a functional impairment related to aging, or may be part of a specific disease such as Parkinson's disease or some other nervous system condition. People with dysphagia complicated by pneumonia have limited feeding and become debilitated, and aspiration pneumonia in these individuals has a high mortality rate at 90 days. Dietary modifications, assistance with feeding, use of postures that facilitate a normal deglutition, rehabilitation, and use of medications to improve swallowing defects are the tools of medicine to overcome the obstacles to swallowing normally and prevent the development of aspiration pneumonia and its consequences.

AbstractAspiration pneumonia (AP) remains a critical health issue, especially among older and hospitalized patients. This review focuses on understanding the epidemiology and pathogenesis of AP, exploring key risk factors, and proposing diagnostic strategies. Aspiration pneumonia is commonly associated with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), where pathogens introduced into the lungs from gastric aspiration cause infection. Several factors, such as oropharyngeal dysphagia, silent aspiration, and poor oral health, contribute to increased risk, especially in frail elderly populations with chronic comorbidities. Diagnostic criteria for AP are not well-defined, complicating accurate diagnosis. Radiographic evidence of pulmonary infiltrates, history of aspiration, and clinical symptoms, such as cough and fever, guide diagnosis, but the absence of specific biomarkers remains a challenge. Furthermore, the microbiome of the lung, which shares characteristics with the oropharyngeal flora, plays a pivotal role in the development of infection. The incidence of AP is likely to increase given the growing elderly population with factors predisposing them to aspiration. It is one of the most common types of pneumonia in older adults, with its prevalence estimated to range from 5% to 24% in cases of CAP admissions. This revision highlights the growing need for comprehensive diagnostic tools and treatment protocols for AP, especially in high-risk populations such as the elderly and those in long-term care. Understanding the underlying mechanisms and the role of silent aspiration can improve prevention strategies and reduce morbidity and mortality in these vulnerable groups.

AbstractAspiration following anesthesia is a major patient issue and a difficulty for anesthesiologists. Aspiration syndromes are more common than anticipated, and the condition is frequently undetected. Clinical signs are often dictated by the characteristics of aspiration, such as the infectivity of the material, its volume, and the severity of the underlying clinical condition. Pulmonary aspiration can cause an acute or persistent inflammatory response in the lungs and upper airways that can be complicated by tracheobronchitis, aspiration pneumonia, aspiration pneumonitis, acute respiratory distress syndrome, and subsequent bacterial infection due to particle, acid, and bacteria-related processes. Aspiration during anesthesia, while relatively rare, poses significant risks for patient morbidity and mortality. Chemical and bacterial aspiration provide distinct diagnostic and management issues. Preventive strategies such as a complete preoperative risk assessment, adherence to fasting rules, proper patient positioning, and the use of protective airway devices are critical in reducing aspiration risk. In addition, drugs such as proton pump inhibitors can help lower stomach acidity and volume. Innovations in monitoring techniques, better training, and awareness activities are critical to enhancing aspiration event management. Given the importance of this entity, this narrative review sought to make an updated overview of the management of aspiration after anesthesia: chemical versus bacterial, differential diagnosis, management, and prevention.

AbstractAspiration-related syndromes comprise a broad spectrum of diseases affecting the airways and lung parenchyma resulting from inadvertent entry of oropharyngeal or gastric contents into the respiratory tract. The diagnosis can be challenging given lack of self-reported symptoms and unwitnessed or silent aspiration events. Aspiration is a common finding in healthy individuals suggesting that host defenses play a critical role in the pathophysiology. In the absence of strict criterion, a high index of suspicion is necessary based on recognition of established risk factors and identification of characteristic imaging findings. Conditions predisposing to altered levels of consciousness and neuromuscular weakness can lead to dysphagia, impaired cough reflux, and subsequent aspiration. The most salient feature on imaging is the anatomic location of the abnormalities, with the superior segments of the lower lobes and posterior segments of upper lobes involved in the recumbent position, and basilar segments of lower lobes in the upright position. Acute syndromes include pneumonia, pneumonitis, and foreign body aspiration. In the more indolent form of aspiration, bronchiectasis, diffuse bronchiolitis, and interstitial lung disease can develop. A detailed understanding of associated radiographic findings for these syndromes can help to implicate aspiration as the cause for imaging abnormalities and ultimately optimize patient management.

AbstractAspiration pneumonia refers to the process of alveolar inflammation induced by the inhalation of oropharyngeal secretions into the lower respiratory tract. Predisposing factors comprise swallowing dysfunction, impaired cough reflex, and degenerative neurological diseases. Accumulating evidence projects a fading contribution of anaerobic bacteria in aspiration pneumonia at the expense of Gram-negative bacilli, with Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, becoming the predominant organisms recovered from respiratory specimens. Aspiration of oropharyngeal secretions colonized with respiratory pathogens induces a profound disequilibrium of the lung microbiota resulting in a state of dysbiosis. Understanding this complex temporal variability between microbiome–host associations was only made possible with the introduction of metagenomic sequencing. In this narrative review, we summarize existing knowledge and elaborate on the evolving microbiology of aspiration pneumonia including the link between oral microbiome and pulmonary aspiration. We also highlight the progress and challenges in instituting microbiome-targeted strategies for preventing and treating the sequelae of aspiration pneumonia.