Current Respiratory Medicine Reviews - Volume 20, Issue 4, 2024

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.

Cystic Fibrosis (CF) is a fatal hereditary condition marked by thicker mucus production, which can cause problems with the digestive and respiratory systems. The quality of life and survival rates of CF patients can be improved by early identification and individualized therapy measures. With an emphasis on its applications in diagnosis and therapy, this paper investigates how Artificial Intelligence (AI) is transforming the management of Cystic Fibrosis (CF). AI-powered algorithms are revolutionizing CF diagnosis by utilizing huge genetic, clinical, and imaging data databases. In order to identify CF mutations quickly and precisely, machine learning methods evaluate genomic profiles. Furthermore, AI-driven imaging analysis helps to identify lung and gastrointestinal issues linked to cystic fibrosis early and allows for prompt treatment. Additionally, AI aids in individualized CF therapy by anticipating how patients will react to already available medications and enabling customized treatment regimens. Drug repurposing algorithms find prospective candidates from already-approved drugs, advancing treatment choices. Additionally, AI supports the optimization of pharmacological combinations, enhancing therapeutic results while minimizing side effects. AI also helps with patient stratification by connecting people with CF mutations to therapies that are best for their genetic profiles. Improved treatment effectiveness is promised by this tailored strategy. The transformational potential of artificial intelligence (AI) in the field of cystic fibrosis is highlighted in this review, from early identification to individualized medication, bringing hope for better patient outcomes, and eventually prolonging the lives of people with this difficult ailment.

Asthma presents with chronic inflammation and airway constriction triggered by allergens or pollution. Inflammatory mediators such as histamine and leukotrienes, released in response to inflammation, prompt bronchoconstriction, contracting the smooth muscles around the airways. This constriction obstructs airflow and worsens symptoms such as coughing, wheezing, and breathlessness. Additionally, airways become hyperresponsive, reacting excessively even to harmless stimuli. Persistent inflammation leads to the production of thick mucus, further blocking airflow and worsening symptoms. Mast cell-released histamine triggers bronchoconstriction, leukotrienes, and prostaglandins (e.g., Interleukin-4, Interleukin-13) and promotes airway inflammation while cytokines drive Th2-mediated immune responses. Current therapies in asthma include long-acting beta agonists, leukotriene modifiers, inhaled corticosteroids, and immunomodulators. Natural products, due to their anti-inflammatory, antioxidant and immunomodulatory properties, have emerged as promising anti-asthmatic candidates. Polyphenols (quercetin, resveratrol, curcumin, etc.) and Omega-3 fatty acids offer anti-inflammatory benefits by suppressing cytokines and oxidative stress. Natural products intervene at various levels of these pathways. Quercetin inhibits the release of mast cell histamines, alleviating bronchoconstriction. Curcumin suppresses Th2 cytokines, mitigating the allergic response. Omega-3 fatty acids modulate leukotriene and prostaglandin production, reducing airway inflammation. This review concludes that natural phytobioactives have potential in asthma management due to their complex mechanisms that target various immuno-inflammatory mediators.

Background: Bronchoscopy and CT thorax are the most common investigations utilized to screen and diagnose lung cancer. Their individual utility in diagnosing lung cancer has been described affirmatively in existing literature. Studies correlating the airway characteristics of the two modalities in lung cancer are limited. Objectives: To analyze and characterize lung lesions bronchoscopically and correlate the same radiologically by CT of the thorax and thus assess its positive predictive value. Methods: In this prospective study, 56 consecutive adults who presented to the Respiratory Medicine Department at a tertiary care hospital in South India from November 2018 to June 2020, having Clinico-radiological suspicion of malignancy and fulfilling study criteria, were recruited. They were subjected to CECT of thorax and bronchoscopy. All bronchoscopic procedures were performed using a protocolized number of passes for biopsy. The baseline demographic and clinical data, findings of bronchoscopy and CT and biopsy reports were recorded. Cohen's kappa coefficient was used to estimate the agreement of findings on the two modalities. Statistical analysis was performed using SPSS software. Results: Bronchoscopy was normal in 22.14% of cases, the corresponding CTs also revealed normal airway. Bronchoscopy revealed airway lesions in 78.6% of cases; the corresponding CT revealed airway abnormalities in only 46.41% of cases; among these, 52.1% of cases revealed an exophytic growth. There was fair strength of agreement for the two modalities in the detection of airway lesions of lung cancer. (k = 0.38, p = <0.001). CECT thorax has a negative predictive value of 44%, a sensitivity of 59.1% and a specificity of 100% at 95% CI in the detection of airway lesions. Conclusion: CT may not be definitive in the evaluation of lung cancer, especially in those with central disease. A combination of the two modalities may improve the diagnostic outcome in patients with lung cancer.

Background: Pulmonary edema (PE) is the result of an abrupt increase in hydrostatic pressure in the pulmonary capillaries that leads to leakage of fluid through microvascular endothelial cells. This leads to a disruption of gas exchange in the lungs. Aims: This meta-analysis aimed to determine the diagnostic accuracy of lung ultrasonography (LUS) in pulmonary edema. Methods: A systematic search was conducted using a strategy based on these search terms (Lung ultrasonography, pulmonary edema, diagnostic accuracy); we searched PubMed, Google Scholar, and the Cochrane Library. Out of 1029, 14 prospective cross-sectional and observational studies with 2239 patients who reported the sensitivity and specificity of lung ultrasonography in diagnosing pulmonary edema were selected. For inclusion and data extraction, an independent review of citations was carried out. The data obtained were analyzed using SPSS, RevMan 5.3, and Stata 14.0 software. A quality assessment was conducted using the QUADAS-2 tool. The reference gold standard was the final clinical diagnosis according to chest radiography, B-type natriuretic peptide, and/or physical examination in dyspneic patients. Results: The overall sensitivity and specificity of lung ultrasonography in the diagnosis of pulmonary edema were 0.86 (95% CI, 0.81-0.90) and 0.91 (95% CI, 0.90-0.93), respectively, with a Younden index of 77.8%. The area under the receiver operating characteristic (ROC) curve was 0.889. Conclusion: The overall diagnostic odds ratio was 68.86. The results of this meta-analysis suggest that lung ultrasonography is an effective non-invasive technique in the diagnosis of acute pulmonary edema with rapid bedside examination and immediate interpretation.

Background: Congenital tracheal stenosis is defined as the narrowing of the airway lumen due to the abnormal formation of complete tracheal cartilage rings. It may present with different clinical pictures, depending on the range and extent of stenosis. We present two cases of congenital tracheal stenosis, with a different range of severity and, consequently, different treatment approaches. Case Presentation: We describe the case of a 3-month-old infant with breathing noise that worsened particularly when crying and after nutrition. He presented a congenital funnel-shaped tracheal stenosis with an associated tracheal bronchus, which was treated endoscopically with an endobronchial stent. The second presented case is of a newborn who presented severe respiratory distress and inspiratory stridor in the first hours of life. A congenital cylindrical tracheal stenosis was diagnosed and it was treated surgically through slide tracheoplasty. Discussion: These two cases showed us that congenital tracheal stenosis can present with a very variable clinical picture. Thus, according to clinical presentation, different treatments can be considered. Conclusion: We underline the importance of considering congenital tracheal stenosis in the differential diagnosis of prolonged wheezing and recurrent airway infections.

Background: Cystic Fibrosis (CF), is the most common, life-limiting, single-gene disease affecting the Caucasian population, with a reported incidence of1/3500 births. It is inherited in an autosomal recessive fashion and its diagnosis is notably challenging, since in several cases CF may not be detected by the newborn screening test and the sweat test, which are frequently reported negative of with doubtful results, especially in cases with atypical symptoms at onset or with uncommon mutations or polymorphisms. Case Presentation: In this case, we present a case of CF presented with recurrent wheezing, reporting multiple negative or borderline sweat tests. The genetic evaluation revealed delta F508 (CF- causing) and heterozygous poly T5 polymorphism TG11 (TG)11T5. Conclusion: The importance of this case lies in the recognition of wheezing as a symptom and not as a disease, thus many conditions such as CF have to be considered in its diagnostic process. Finally, it is of utmost importance to bear in mind that many mutations or polymorphisms might evade newborn screening and sweat tests.

Background: Middle lobe syndrome (MLS) is a distinct clinical and radiographic entity characterized by recurrent or chronic collapse of the middle lobe of the right lung, but it can also involve the lingula of the left lung. Case Study: This study presents a rare case of MLS caused by a vascular ring never described in the literature until now and provides physicians with the clinical and instrumental tools in order to early recognize and promptly treat this condition. The case report was reported according to CARE guidelines. A literature research on PubMed/MEDLINE was also performed using the MeSH terms “Middle lobe syndrome OR MLS AND double aortic arch” “Middle lobe syndrome OR MLS AND vascular rings”. No case described in the literature was found. In most cases, MLS presents non-specific respiratory symptoms, which unfortunately is responsible for the diagnostic delay that patients with this pathology often suffer. The diagnostic delay is estimated to be 8 months (range 3 to 36 months). A history of dysphagia and regurgitation can be indirect signs of a vascular compression, such as vascular rings, which can cause MLS. Conclusion: To date, the reported case is the only case in the literature of MLS caused by double aortic arch. The key point for the diagnosis of MLS is diagnostic suspicion. Early recognition of MLS is essential to quickly start a targeted therapeutic program avoiding the persistence of vicious circle atelectasis-recurrent respiratory infections, and this could significantly improve the long-term outcome of these patients.

Introduction: Endobronchial tuberculosis is a challenging disease to diagnose, characterized by infection of the tracheobronchial tree caused by Mycobacterium Tuberculosis. The clinical presentation of endobronchial tuberculosis is nonspecific and variable, making it difficult to identify. Case Report: This report explores the challenges faced during the diagnosis of endobronchial tuberculosis by a 63-year-old female patient presented with a chronic cough lasting over two months. Her chest X-ray revealed an inhomogeneous opacity in the left middle zone, accompanied by an air-bronchogram. Conventional sputum samples and other tests returned negative results. A high-resolution chest CT scan was almost complete consolidation in the lingular subsegment. A comprehensive re-evaluation was recommended in this case due to slow re-solving or non-resolving pneumonia. The histopathological examination of the biopsy sample revealed granulomatous inflammation with necrosis and lymphocytic infiltration, strongly indicating bronchial tuberculosis. The Hain test and MGIT culture confirmed the presence of Mycobacterium tuberculosis. Conclusion: Diagnosing endobronchial tuberculosis can be challenging due to its nonspecific and variable clinical presentation. High-resolution CT scans provide valuable insights, but the absence of typical findings can complicate the diagnosis. Bronchoscopic biopsy proved to be the most reliable method for diagnosing endobronchial tuberculosis in this case. Early and accurate diagnosis is crucial for initiating appropriate treatment and preventing complications.