20S-Ginsenoside Rh2, the major bioactive saponin in Panax notoginseng flowers, ameliorates cough by inhibition of NaV1.7 and TRPV1 channel currents and downregulation of TRPV1 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng flowers, which are the buds of the traditional Chinese medicinal herb Sanqi, are widely used in China for their cough-ameliorating properties, with demonstrated therapeutic effects in the treatment of both acute and chronic coughs. However, both the antitussive mechanism and active compound basis of P. notoginseng flowers remain poorly understood. AIM OF THE STUDY: We investigated the antitussive effects of P. notoginseng flowers, identified the bioactive constituents responsible for alleviating cough symptoms, and elucidated the underlying pharmacological mechanisms. MATERIALS AND METHODS: We analyzed the major chemical constituents of aqueous extracts of P. notoginseng flowers using liquid chromatography-mass spectrometry and quantitatively analyzed the key component, 20S-ginsenoside Rh2, using high-performance liquid chromatography. Using a cough reflex model in healthy mice and an ovalbumin-induced, highly sensitive guinea pig cough model, we verified the suppressive effects of P. notoginseng flowers and their saponin constituents on coughing. Furthermore, we explored the mechanisms of action of the key ion channels, NaV1.7 and TRPV1, using whole-cell patch-clamp techniques and molecular docking. Finally, the therapeutic mechanisms of P. notoginseng flowers on pathological cough were revealed using hematoxylin and eosin staining, immunohistochemistry, and western blotting. RESULTS: The active components of P. notoginseng flowers were primarily protopanaxadiol-type saponins, among which 20S-ginsenoside Rh2 had the highest content (51.46 mg/g). In the mouse model, P. notoginseng flowers exhibited antitussive effects comparable to those of pentoxyverine citrate. Although its main saponin component, 20S-ginsenoside Rh2, showed slightly weaker effects, it still demonstrated concentration-dependent inhibition of channel activity. The whole-cell patch-clamp technique and virtual molecular docking showed that Rh2 might exert its effects by directly binding to the NaV1.7 and TRPV1 channels. In the guinea pig model, P. notoginseng flowers and their saponin components not only reduced cough frequency and prolonged the latency period before cough onset, but also significantly inhibited tracheal and pulmonary inflammation and the overexpression of TRPV1. CONCLUSIONS: 20S-Ginsenoside Rh2, the major bioactive saponin in P. notoginseng flowers, exhibits potent antitussive effects. The potential mechanism of action of 20S-Ginsenoside Rh2 in the treatment of cough may involve inhibiting NaV1.7 and TRPV1 channel currents through direct binding to core protein active sites and downregulating TRPV1 expression.

Effect of Plantago major on cough severity in acute bronchitis: A double-blind randomized clinical trial.

Background: Treatments for acute bronchitis is usually a supportive care to relieve upper respiratory symptoms. This study aimed to evaluate the effect of Plantago major syrup (PMS) on cough severity in acute bronchitis. Methods: Patients (20-75 years-old) referred to the clinic of infectious diseases in Ayatollah Rouhani Hospital, Babol, Iran with a complaint of cough and the Bronchitis Severity Scale (BSS) ≥5 entered the study. The patients randomly received PMS or placebo 30 ml/day for 10 days. Patients were visited before treatment and on days 5 and 10 after treatment. The primary outcome was BSS score and secondary outcome was the life quality that was measured by means of the Persian version of the Leicester Cough Questionnaire (LCQ) at the first visit and on the 10th day. Results: Of the 121 patients diagnosed with acute bronchitis, 80 eligible patients (42.87±11.75 years-old) were randomly divided into PMS and placebo groups. The BSS score in the PMS group after 10 days was significantly lower than that of the placebo group (P=0.001). Frequency of cough (P=0.001), sputum production (P=0.005), and chest wall pain (P=0.008) were significantly lower in the PMS group than in the placebo group. In terms of quality of life, all items, including psychological, physical, and social domains, as well as total scores, were altered significantly in the PMS group compared to placebo. During monitoring of side effects, no significant adverse effects were stated in either group. Conclusion: The study indicates the palliative effects of PMS in relieving the symptoms of acute bronchitis and improving quality of life.

Analysis of Influencing Factors and Construction of Predictive Model for Persistent Cough After Lung Cancer Resection Under Thoracoscopy.

Objective: This study aims to explore the influencing factors of cough after pulmonary resection (CAP) after thoracoscopic lung resection in lung cancer patients and to develop a predictive model. Methods: A total of 374 lung cancer patients who underwent lung resection in our hospital from March 2020 to October 2023 were randomly divided into a modeling group (n=262) and a validation group (n=112). Based on the occurrence of CAP in the modeling group, the patients were divided into a CAP group (n=85) and a non-CAP group (n=177). Multivariate Logistic regression analysis was used to identify the influencing factors of CAP in lung cancer patients. A nomogram model for predicting the risk of CAP was constructed using R4.3.1. The consistency of the model's predictions was evaluated, and a clinical decision curve (DCA) was drawn to assess the clinical utility of the nomogram. The predictive performance of the model was evaluated using ROC curves and the Hosmer-Lemeshow test. Results: Multivariate Logistic regression analysis showed that smoking history (OR=6.285, 95% CI: 3.031-13.036), preoperative respiratory function training (OR=20.293, 95% CI: 7.518-54.779), surgical scope (OR=20.667, 95% CI: 7.734-55.228), and peribronchial lymph node dissection (OR=5.883, 95% CI: 2.829-12.235) were significant influencing factors of CAP in lung cancer patients (P<0.05). ROC curves indicated good discriminatory power of the model, and the Hosmer-Lemeshow test showed a high degree of agreement between predicted and actual probabilities. The DCA curve revealed that the nomogram model had high clinical value when the high-risk threshold was between 0.08 and 0.98. Conclusion: The nomogram model based on smoking history, preoperative respiratory function training, surgical scope, and peribronchial lymph node dissection has high predictive performance for CAP in lung cancer patients. It is useful for clinical prediction, guiding preoperative preparation, and postoperative care.

Differential diagnosis of mediastinal cysts: a case series.

BACKGROUND: Mediastinal cysts are common mediastinal lesions in which diagnostic and therapeutic choices are not always unambiguously presented. Usually, these cysts are asymptomatic and detected by coincidence. The question remains whether, if symptoms are present, the cyst is responsible and whether it should be treated. Unfortunately, there is a lack of standardised guidelines concerning diagnostic, therapeutic management and follow-up. CASE SUMMARY: In this case series we reported five patients with mediastinal cysts. All patients received a thoracic CT during the initial diagnostic assessment. Four out of five patients were symptomatic and were surgically treated during a uniportal video-assisted thoracoscopy. One patient was asymptomatic and receives a biennial follow-up. Most often, histopathological examination confirmed the already presumed type of non-neoplastic mediastinal cyst based on anatomical location and tissue characteristics (one thymic cyst, one bronchogenic cyst and two pericardial cysts). Except for one patient, all surgically treated patients experienced improvement in symptoms. CONCLUSION: Regarding diagnosis and treatment of this entity, a systematic approach in accordance with the most recent literature is important. The diagnosis can only be confirmed on histopathological examination, but several imaging techniques, with contrast-enhanced CT as the first-choice technique, could guide the differential diagnosis. In large, symptomatic cysts or present potential malignant features, surgical removal is indicated. This case series encourages further substantial research concerning the selection and timing of therapy.

Effects of Azithromycin on Blood Inflammatory Gene Expression and Cytokine Production in Sarcoidosis.

INTRODUCTION: In sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis. METHODS: Blood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP. RESULTS: Differential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers. CONCLUSION: Blood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood. TRIAL REGISTRATION: EudraCT 2019-000580-24 (17 May 2019).

Small airway inflammation in atypical asthma.

Background: Less attention has been paid to the pathophysiological changes in atypical asthma such as cough variant asthma (CVA) and chest tightness variant asthma (CTVA). The obstruction of large and small airways is the important component in the development of asthma. We investigated whether small airway inflammation (SAI) induced small airway dysfunction (SAD) in these atypical asthmatics. Methods: Six hundred and eighty-six patients were enrolled and analyzed in the study. The partitioned airway inflammation was assessed by fractional exhaled nitric oxide (FeNO), such as FnNO, FeNO50, FeNO200, and calculated alveolar fraction of exhaled NO (CaNOdual). Correlations between exhaled NOs and SAD-related variables were assessed, whereas cell classification was evaluated by Spearman's rank tests. Classic asthma, CVA, and CTVA about potential risk were conducted using binary logistic regression models. Results: The whole airway inflammation increased in classic and atypical asthma than controls, whereas the central and peripheral airway inflammation in the CVA and CTVA groups increased compared with the classic asthma group. Smoking exposure was found to increase the central and peripheral airway inflammation in patients with asthma. The exhaled NO of FeNO50 and FeNO200 was associated with SAD in classic asthma, but not in CVA and CTVA. FeNO200 was the main risk (adjusted odds ratio [OR], 1.591; 95 % CI, 1.121-2.259; P = .009) in classic asthma and (adjusted OR, 1.456; 95 % CI, 1.247-1.700; P = .000) in CVA. The blood eosinophil levels were correlated with FeNO50 and FeNO200 in classic asthma and atypical asthma. Conclusion: More severe inflammatory process was present in central and peripheral airways in CVA and CTVA, which might reflect a pre-asthmatic state. SAI was the predominant risk factor in the development of asthma before SAD.

A Case Report on the Trilogy of Yellow Nail Syndrome: Yellow Nails, Pleural Effusion, and Lymphedema.

Yellow nail syndrome is a rare medical syndrome characterized by the combination of a triad of yellow nails, recurrent pulmonary manifestations, and lymphedema. All three features of the triad may not be present synchronously. The diagnosis is made clinically once other causes have been excluded. Typically, it occurs in individuals who are 50 years old and above. We report a case of yellow nail syndrome in a 62-year-old male who presented with recurrent episodes of difficulty breathing due to pleural effusion. Further examination revealed pitting edema of the bilateral lower extremities. In the later encounter, his nail was found to be yellowish. Excluding other diagnoses like heart failure, fungal infections, autoimmune diseases, and lung cancer, with a typical triad, a diagnosis of yellow nail syndrome was made. He was managed with pleural fluid tapping for pleural effusion, compression stockings for leg edema, and vitamin E for nail changes. The study also intends to highlight current treatment options and alert physicians of this syndrome with such typical findings.

SARS­CoV­2 infection exacerbates diaphragmatic eventration: A case report.

Adult congenital localized diaphragmatic eventration (DE) is an uncommon condition that, due to the absence of notable symptoms, is often ignored and is consequently not frequently treated following diagnosis. Furthermore, the progression of localized DE into complete DE is rare. The recent coronavirus disease 2019 pandemic has placed a strain on global health care systems, including those in China, and exacerbated several underlying medical complications and diseases. This has resulted in a rapid progression of underlying diseases and even death in cases of diabetes or pre-existing respiratory diseases and other chronic conditions. The present study describes the case of a patient with congenital localized DE that progressed to complete DE following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient had a medical history of localized DE with persistent cough, chest tightness and abdominal distension following infection with SARS-CoV-2. Chest X-ray and computed tomography examinations confirmed the diagnosis of complete DE on the left side. Therefore, the patient underwent thoracic surgery for left-sided diaphragmatic plication. At the 6-month follow-up visit, the patient had recovered well and did not show any complications. Overall, the present study demonstrated that SARS-CoV-2 infection exacerbated the progression of left-sided congenital localized DE, which had no obvious symptoms, to complete DE accompanied by severe symptoms.

Postoperative exacerbated cough hypersensitivity syndrome induces dramatic respiratory alkalosis, lactatemia, and electrolyte imbalance.

BACKGROUND: The perioperative management of patients with chronic cough or cough hypersensitivity syndrome and its sometimes severe effects is currently under-researched and under-reported. CASE PRESENTATION: A 46-year-old female patient with a history of chronic cough and Cough Hypersensitivity Syndrome. After laparoscopic hiatoplasty and anterior fundoplication under general anesthesia, experienced a pronounced exacerbation of coughing symptoms. Despite prompt and extensive treatment involving antitussives, inhalants, anxiolytics, and sedatives, the symptoms remained uncontrollable. Within a few hours, the patient developed a respiratory alkalosis with severe and life-threatening electrolyte shift (pH 7.705, pCO2 1.72 kPa, K+ 2.1 mmol/l). Lactatemia lasted for more than 12 hours with values up to 6.6 mmol/l. Acute bleeding, pneumothorax, and an acute cardiac event were ruled out. Deep analgosedation and inhalation of high-percentage local anesthetics were necessary to manage the clinical symptoms. CONCLUSIONS: This case highlights the challenging nature of chronic cough and hypersensitivity syndrome perioperatively. A tailored anesthesiologic approach, exclusion of other provoking medical problems, and knowledge of possible management and treatment options are key.

A rare case of foreign body inhalation masquerading as calcification in the right upper lobe suggestive of tuberculosis.

Airway foreign bodies are a common clinical emergency, predominantly occurring in children, with adults less frequently affected. Airway foreign bodies can cause a variety of symptoms, with adults more commonly presenting with cough, a factor that often leads to misdiagnosis or missed diagnosis. Due to anatomical features, most foreign bodies are more likely to be aspirated into the right bronchus, especially the right lower and middle bronchi, with the right upper lung less commonly involved. Here, we report a case where a small, sharp foreign body (a chicken bone) became lodged at the opening of the right upper lobe bronchus in a healthy middle-aged male. Initially, the foreign body was mistaken for an old tuberculous calcification due to recurrent coughing and shortness of breath over two years, misdiagnosed as chronic obstructive pulmonary disease. Eventually, the foreign body was successfully removed. Therefore, the possibility of foreign body inhalation should not be overlooked in adult patients presenting with recurrent cough symptoms.

Association of SLCO1B1 gene variants with angiotensin-converting enzyme inhibitor-induced cough in a Pakistani hypertensive cohort.

Background: Angiotensin-converting enzyme inhibitors (ACEIs) are prescribed for individuals with high cardiovascular (CV) risk; however, persistent cough limits the use of ACEIs in a large number of patients. The current study aimed to identify the genetic variants in the SLCO1B1 gene that might be associated with ACEI-related cough in a Pakistani hypertensive population. Methods: A prospective cohort study was conducted at a tertiary care hospital in Pakistan. A total of 74 patients who had been treated with ACEIs were recruited through a convenient sampling method. The study was approved by the Institutional Review Board & Ethics Committee of the Shifa International Hospital, Islamabad. Patients provided 2 ml of blood for sequencing after signing informed consent. Partial gene sequencing of SLCO1B1 was carried out to find single nucleotide polymorphisms (SNPs) and haplotypes. Results: It was found, through a structured questionnaire, that thirty-eight (38) patients experienced cough within 2 weeks of ACEI administration and were considered as a case group (cough), and thirty-six (36) patients were considered as a control group (no cough). The incidence of cough was 51%. We found six different SNPs and 9 haplotypes in the partial gene sequences of SLCO1B1. Haplotype H4 was associated significantly with cough after adjusting for sex and smoking status. Other SNPs and haplotypes were not significantly associated with ACE-Is-induced cough. Conclusion: These findings emphasize the significance of SLCO1B1 genetic variants, specifically H4, as a potential predictor of ACEI-induced cough. It could be included in clinical practice as a possible risk factor for ACEI-induced cough once confirmed in larger clinical trials with bigger sample sizes. The replication of these findings in larger and more diverse populations is likely to contribute to the therapeutic use of ACEIs by predicting ACEI-induced cough.

Laryngopharyngeal Reflux Pathophysiology, Clinical Presentation, and Management: A Narrative Review.

Laryngopharyngeal reflux (LPR) is a common and often misinterpreted clinical entity responsible for various symptoms affecting the upper aerodigestive tract. This narrative literature review aims to review the pathophysiology, symptoms, and management of LPR, emphasizing the emerging understanding of gastric content reflux in aerodigestive tissue irritation. Understanding the pathophysiology of LPR will allow general practitioners and specialists to accurately recognize and treat a condition that causes substantial morbidity in the affected patients. Using evidence-based findings from randomized controlled trials, clinical studies, and meta-analyses, the present investigation aims to outline and unify previous research into LPR. A review of anatomical structures, pathogenic mechanisms, endoscopic findings in LPR, and clinical manifestations and treatment options are also discussed. Though controversy around the diagnosis and management of LPR persists, emerging research in cellular damage and diagnostic tools promises to provide increasingly accurate and reliable modalities for characterizing LPR. Hopefully, future research will unify the field and provide overarching guidelines for both primary care and specialists. The present investigation provides an integrated perspective on LPR, a clinically prevalent and complex disease.

Amygdalar involvement in respiratory dysfunction.

The brainstem has long been recognized as the major respiratory control center, but it has become increasingly appreciated that areas upstream of the brainstem modulate respiration and airway defensive behaviors. This review aims to define the role of the amygdala, a key temporal brain region essential for limbic function, in respiration and airway defenses. We summarize literature describing roles for the amygdala in control of respiration, swallow, cough, airway smooth muscle contraction, and mucus secretion. We emphasize the need to understand how the amygdala regulates these functions both at a local scale and network scale and identify knowledge gaps for current and future investigations. Lastly, we highlight literature suggesting that amygdala dysfunction may contribute to respiratory dysfunction.

A case report of massive pulmonary tuberculosis and newly diagnosed systemic lupus erythematosus with complications.

The diagnosis of extensive pulmonary tuberculosis, especially in young people, should take into account the possibility of an associated systemic autoimmune disease. Infections remain an important cause of morbidity and mortalityin systemic lupus erythematosus. This case illustrates the importance of recognizing the association of systemic autoimmune diseases and infections and the need for a multidisciplinary approach.

Diagnosed and undiagnosed cough-related stress urinary incontinence in women with refractory or unexplained chronic cough: Its impact on general health status and quality of life.

Background: Stress urinary incontinence (SUI) is common in women with chronic cough but may be overlooked. Objective: To determine the frequency of underdiagnosis of cough-related SUI and its impact on women's general health status and quality of life (QoL). Methods: Data were analyzed for 147 women with refractory/unexplained chronic cough. Relevant details were collected from clinical charts and a patient-completed survey. General health status was assessed using the EuroQoL visual analogue scale (EQ-VAS) and QoL with the cough-specific Leicester Cough Questionnaire (LCQ). Results: Women were classified into diagnosed (n = 32; 21.8%) or undiagnosed (n = 33; 22.4%) cough-related SUI, and no SUI (n = 82; 55.6%) groups. Women with versus without cough-related SUI perceived poorer health status and greater impact of cough on everyday lives. Mean LCQ scores were significantly lower in cough-related SUI groups versus no SUI group. In multivariate analysis, the presence of cough-related SUI was significantly associated with lower EQ-VAS and LCQ scores. Conclusion: In our cohort, 44% of women had cough-related SUI, and half were undiagnosed. Irrespective of diagnosis, impairment to everyday lives and QoL was similar. Diagnosing cough-related SUI may identify additional patients who can benefit from therapies to suppress cough and improve QoL.

Pulmonary infection by Mycobacterium riyadhense: first case report in United Arab Emirates.

Mycobacterium riyadhense is an emerging slowly growing species that belongs to the group of nontuberculous mycobacteria (NTM) with approximately 20 cases reported worldwide. We highlight the first case of pulmonary infection by Mycobacterium riyadhense in United Arab Emirates (UAE). A 44-year-old female presented with chronic productive cough; a bronchial breathing pattern was appreciated on auscultation of her right upper lung. She was treated multiple times with allergic medications and antibiotics. Thorough investigations revealed Mycobacterium riyadhense and antitubercular drugs were started, eventually she was cured, however she had multiple relapses later. This case report holds a significant potential to make considerable contribution to the diagnosis of NTM, primarily because it presents the first documented case in UAE, as well as insights on how to address possible similar cases in the future.

Content validity of the Leicester Cough Questionnaire in adults with refractory or unexplained chronic cough: a qualitative interview study.

BACKGROUND: Chronic cough, a cough lasting >8 weeks, includes refractory chronic cough (RCC) and unexplained chronic cough (UCC). Patient-reported outcome (PRO) measures are needed to better understand chronic cough impacts that matter most to patients. The 19-item Leicester Cough Questionnaire (LCQ), an existing PRO measure of chronic cough, assesses impacts of cough across physical, psychological, and social domains. However, the content validity of the LCQ evaluating these concepts in patients with RCC/UCC had not been established. OBJECTIVES: To evaluate the content validity of the LCQ in patients with RCC/UCC. DESIGN: A cross-sectional, qualitative interview study. METHODS: First, previously completed qualitative interview results in adults with RCC/UCC (N = 30) were evaluated and mapped to LCQ concepts. Next, a clinical cough expert reviewed each LCQ item and assessed the salience of its concepts for patients with RCC/UCC. Finally, semistructured interviews-including both concept elicitation and cognitive debriefing-were conducted in adults with RCC/UCC (N = 20) to elicit a comprehensive set of participant experiences and to assess the appropriateness of using the LCQ in this population. RESULTS: Concepts reported in the past and present qualitative interviews were included across all LCQ items, and most impacts reported to be the "most bothersome" were assessed in the LCQ. In the current study, all participants indicated that reduced cough frequency would be an important treatment target. During cognitive debriefing, each LCQ item was endorsed by ⩾70% of participants. Additionally, participants were generally able to understand, recall, and select a response for each LCQ item. All participants and the clinical expert indicated that the LCQ was appropriate and assessed the impacts most relevant to patients with RCC/UCC. CONCLUSION: Our findings support the content validity of the LCQ and demonstrate that this measure is fit-for-purpose and includes important cough impacts in adults with RCC/UCC.