Alveolar type II cells and pulmonary surfactant in COVID-19 era.

In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.

Upper Airway Cough Syndrome in Pathogenesis of Chronic Cough.

Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing.Upper airway cough syndrome (UACS) - previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.

Non-Reflex Defense Mechanisms of Upper Airway Mucosa: Possible Clinical Application.

The sinonasal mucosa has an essential role in defense mechanisms of the upper respiratory tract. The innate immune system presents the primary defense against noxious microorganisms followed by induction of the adaptive immune mechanisms as a consequence of the presence of pathogens. This well-known activation of adaptive immune system in response to presence of the antigen on mucosal surfaces is now broadly applicated in vaccinology research. Prevention of infectious diseases belongs to substantial challenges in maintaining the population health. Non-invasive, easily applicable mucosal vaccination purposes various research opportunities that could be usable in daily practice. However, the existence of multiple limitations such as rapid clearance of vaccine from nasal mucosa by means of mucociliary transport represents a great challenge in development of safe and efficient vaccines. Here we give an updated view on nasal functions with focus on nasal mucosal immunity and its potential application in vaccination in nearly future.

Nasal nitric oxide in healthy adults - reference values and affecting factors.

Nitric oxide (NO) is an important endogenous mediator with significant role in the respiratory system. Many endogenous and exogenous factors influence the synthesis of NO and its level is significantly changed during the inflammation. Analysis of nasal nitric oxide (nNO) is not validated so far as the diagnostic method. There is a lack of reference values with possible identification of factors modulating the nNO levels. In healthy adult volunteers (n=141) we studied nasal NO values by NIOX MINO® (Aerocrine, Sweden) according to the recommendations of the ATS & ERS. Gender, age, height, body weight, waist-to-hip ratio, FEV1/FVC, PEF and numbers of leukocytes, eosinophils, basophils and monocytes were studied as potential variables influencing the levels of nNO. The complexity of the results allowed us to create a homogenous group for nasal NO monitoring and these data can be used further as the reference data for given variables. Because of significant correlation between nNO and exhaled NO, our results support the "one airway - one disease" concept. Reference values of nasal NO and emphasis of the individual parameters of tested young healthy population may serve as a starting point in the non-invasive monitoring of the upper airway inflammation.

Laryngeal Cancer: 12-Year Experience of a Single Center.

Laryngeal cancer is about the twentieth most common cancer in the world and more than 150,000 new cases are diagnosed annually. The aim of the study was to evaluate the history, diagnostics, treatment outcomes, and prognosis in patients with laryngeal cancer in Northern Slovakia. We analyzed retrospectively 227 patients (207 males, 20 females) with laryngeal carcinoma treated in the period 2003-2014 at the Clinic of Otorhinolaryngology and Head and Neck Surgery of the Jessenius Faculty of Medicine and Martin University Hospital in Martin, Slovakia. The majority of patients were in the sixth (38.0 %) and seventh decade of life (30.8 %). Two hundred and seventeen patients (95.6 %) were smokers or ex-smokers. Sixty-six percent of patients were diagnosed with glottic or transglottic carcinoma, related probably to the anatomical structure of the larynx and exposure to inhalation pollutants. It is alarming that the majority of patients with malignant laryngeal disease were admitted to the hospital in advanced stages. In 151 (66.5 %) of patients, the extent of infiltration was T3 or T4, and 156 (68 %) patients were in disease stage III and IV. The incidence and mortality of laryngeal cancer suggest the need to intensify the prevention and to search for an early clinical stage of laryngeal cancer using a targeted screening.

Primary prosthetic voice rehabilitation in patients after laryngectomy: applications and pitfalls.

The use of the tracheoesophageal (T-E) silicone rubber voice prosthesis is the most effective and well-established procedure to restore the voice in patients after laryngectomy. The prosthesis is usually well-tolerated with only minor complications. Severe complications are rare. In this article we present our experience with the prosthetic technique at the Clinic of Otorhinolaryngology and Head and Neck Surgery in University Hospital in Martin, Slovakia between the years 2005-2013 and report a case of a 48-year-old man with secondary prosthesis inserted through a T-E shunt 16 months after laryngectomy. On the 6th day after the insertion, the shunt decayed. After prosthesis removal the tissue defect was sutured. Due to repetitive tissue decay, reconstruction of the trachea and esophagus became necessary. On the 10th day, peritracheoesophageal fistula developed and gastrostomy was performed. Because of intense fibrotic and inflammatory changes, further reconstruction was not indicated. After 6 months, esophageal stenosis occurred and endoscopic dilation under local anaesthesia was performed. The T-E voice prosthesis has become one of the choices for voice rehabilitation following total laryngectomy and may improve the patient's long-term quality of life. The overall risk of severe complications seems relatively low. Nonetheless, some complications might be challenging and might require specific management.

Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle.

Beside alveoli, surface active material plays an important role in the airway physiology. In the upper airways it primarily serves in local defense. Lower airway surfactant stabilizes peripheral airways, provides the transport and defense, has barrier and anti-edematous functions, and possesses direct relaxant effect on the smooth muscle. We tested in vitro the effect of two surfactant preparations Curosurf® and Alveofact® on the precontracted smooth muscle of intra- and extra-pulmonary airways. Relaxation was more pronounced for lung tissue strip containing bronchial smooth muscle as the primary site of surfactant effect. The study does not confirm the participation of ATP-dependent potassium channels and cAMP-regulated epithelial chloride channels known as CFTR chloride channels, or nitric oxide involvement in contractile response of smooth muscle to surfactant.By controlling wall thickness and airway diameter, pulmonary surfactant is an important component of airway physiology. Thus, surfactant dysfunction may be included in pathophysiology of asthma, COPD, or other diseases with bronchial obstruction.

Antitussive effects of nasal thymol challenges in healthy volunteers.

Eighteen healthy volunteers with normal lung function were tested for cough. Before and after nasal administration of thymol (0.025 ml, 10(-3) M) into both nostrils, urge-to-cough, cough threshold, cumulative and total count of coughs per provocation were estimated during standardized and validated capsaicin cough challenge. Nasal thymol challenges induced pleasant olfactory sensation and in 6 out of the 18 subjects also mild cooling sensation. Cough threshold was not influenced when compared with intranasal saline and vehicle challenges (12.5 vs. 13.2 vs. 10.2 µM of capsaicin to induce two or more coughs (C2), respectively), but the total count of coughs after nasal thymol challenge was significantly lower than that obtained after saline or vehicle (19 vs. 20 vs. 14 coughs/provocation, respectively; p<0.05). Importantly, subjects did not report the urge to cough, which appeared to correspond to C2. We conclude that the modulation of cough by thymol is mostly of olfactory origin.

Solitary intrathyroid metastasis of renal cancer.

In general, it is estimated that around 1% of all clinically detectable thyroid cancers are of metastatic origin. With regard to the origin of the metastatic thyroid lesions, the most common primary sites are tumors of kidneys, breast, lungs and gastrointestinal system, and melanomas. Patients with nodular goiter and history of malignancy should be stratified into a high risk category. The authors present a patient with solitary thyroid metastasis from renal clear cell carcinoma 31 and 11 years after left and right nephrectomy and present a comprehensive review of the literature (Fig. 3, Ref. 14).

Thyroid diseases in children and adolescents.

BACKGROUND: Thyroid nodules are relatively rare in children and adolescents and have a prevalence between 0.2%-1.8%. They are more often malignant in children than in adults and thus an early diagnosis is extremely important. OBJECTIVE: The aim of the study was to analyze the group of pediatric patients with nodular thyroid diseases. METHODS: The authors processed the documentation of 66 pediatric patients with nodular thyroid disease who have been surgically treated at the Clinic of Otorhinolaryngology and Head and Neck Surgery, JFM CU and MFH in Martin during 2003-2007. RESULTS: Family history was positive in 32 patients (48.5%). Twenty-three patients (35%) had hyperfunction thyroid disease. Euthyroid status was found in 43 patients (65%). Ultrasonography examination was performed in all patients. Percutaneous aspiration biopsy was performed in 38 patients (58%) and peroperative histology in 40 patients (61%). Technecium (Tc)99m-scintigraphy was performed in 4 patients (6%). CT and MRI examination of the neck and upper mediastinum was indicated in one child. All patients were surgically treated with classical approach after achieving euthyroid stage. Total thyroidectomy was performed in 24 patients, hemithyroidectomy in 41 patients and isthmectomy was done in one patient. No severe postoperative complications were present. CONCLUSION: Thyroid diseases are the second most frequent endocrinopathy in children and adolescents with girls being more frequently affected. It is multidisciplinary problem requiring cooperation of specialists in different fields of medicine. In patients with thyroid diseases not responding to conservative treatment or with clinical signs of mechanical syndrom surgery is a causal therapy (Tab. 3, Ref. 20). Full Text (Free, PDF) www.bmj.sk.

Lung surfactant alterations in pulmonary thromboembolism.

Beside neonatal respiratory distress syndrome, secondary surfactant deficiency may occur in patients with mature lungs. Recent studies revealed quantitative and qualitative changes of lung surfactant in pulmonary thromboembolism (PTE) concerning the total phospholipids content in BAL fluid, alterations in surfactant phospholipids classes and a large-to-small aggregates ratio. Reduced expression of surfactant protein A (SP-A) mRNA and SP-A in lung tissue after pulmonary embolism was found. Serum levels of SP-A were significantly higher in patients with PTE than in other lung diseases, except COPD. Surfactant changes in PTE may result from damage of type II cells by hypoxia, leakage of plasma proteins into the airspaces and/or by reactive oxygen species. They can contribute to lung atelectasis and edema, and a further reduction in oxygen saturation as seen in clinical picture of PTE. Surfactant changes are reliable marker of lung injury that might become a prognostic indicator in patients with pulmonary thromboembolism.

Surgical treatment of primary hyperparathyroidism.

OBJECTIVE: The aim of the study was to evaluate the history, diagnostic procedures, extent and success of the surgical treatment, and possible complications in patients with primary hyperparathyroidism. The authors further discuss the findings in the context of literature data. METHODS: Retrospectively, 48 patients (7 males and 41 females) were analyzed with primary hyperparathyroidism treated between 1999-2006 at the Clinic of Otorhinolaryngology and Head and Neck Surgery JFM CU and FH in Martin at average age of 56 +/- 9 years. RESULTS: In 90%, pHPT was caused by solitary adenoma and in 10% by hyperplasia. Eleven per cent of patients were asymptomatic. Ultrasonography was performed in all and sestamibi scintigraphy in 17 patients. In 3 cases adenoma was localized ectopically. All patients were treated with traditional bilateral cervical approach. Complications excluding transient hypocalcemia (one-side paralysis, subcutaneous haematoma and inflammation) were present in < 1 % of patients. CONCLUSION: Surgical removal of hormonally active tissue is safe and causal treatment of primary hyperparathyroidism with high success rate (Tab. 4, Ref. 21). Full Text (Free, PDF) www.bmj.sk.

Differences in oxidative status, lung function, and pulmonary surfactant during long-term inhalation of medical oxygen and partially ionized oxygen in guinea pigs.

Inhalation of partially ionized oxygen may have less adverse effects on lung functions than medical oxygen. Guinea pigs inhaled air, 100% molecular medical oxygen (O(2)mol), partially negatively (O(2)neg) or positively (O(2)posit) ionized oxygen during 17 and 60 h. After 17 h, dityrosines, markers of oxidative injury, in lung homogenate increased in O(2)neg and decreased in O(2)posit groups vs. controls. After 60 h, dityrosines rose after inhalation of O(2)mol and O(2)neg, but not in the O(2)posit group. Lysine-LPO products increased and lung wet/dry weight ratio decreased in O(2)mol and O(2)neg, and not in O(2)posit group. Relative neutrophil count in BALF was elevated in all oxygen-treated groups with lower numbers in O(2)posit vs.O(2)mol and O(2)neg groups. After 60 h, surfactant activity was better in O(2)posit vs. O(2)mol group. In conclusion, long-term inhalation of partially positively ionized oxygen is associated with less oxidative stress, milder lung inflammatory response, and better surfactant activity than molecular or negatively ionized oxygen.

Early and late allergic phase related cough response in sensitized guinea pigs with experimental allergic rhinitis.

Cough is a common and important symptom of asthma and allergic rhinitis. Previous experimental evidence has shown enhanced cough sensitivity during early phase of experimental allergic rhinitis in guinea pigs. We hypothesized that airway inflammation during the late phase response after repeated nasal antigen challenge may affect the afferent sensory nerve endings in the larynx and tracheobronchial tree and may also modulate cough response. In the present study we evaluated the cough sensitivity during a period of early and late allergic response in sensitized guinea pigs after repeated nasal antigen challenges. Forty-five guinea pigs were sensitized with ovalbumin (OVA). Four weeks later 0.015 ml of 0.5 % OVA was intranasally instilled to develop a model of allergic rhinitis that was evaluated from the occurrence of typical clinical symptoms. Animals were repeatedly intranasally challenged either by OVA (experimental group) or by saline (controls) in 7-day intervals for nine weeks. Cough was elicited by inhalation of citric acid aerosols. Cough was evaluated at 1 or 3 h after the 6th nasal challenge and 17 or 24 h after the 9th nasal challenge. The cough reflex was significantly increased at 1 and 3 h after repeated nasal challenge in contrast to cough responses evoked at 17 and 24 h after repeated nasal challenge. In conclusion, enhanced cough sensitivity only corresponds to an early allergic response after repeated nasal challenges.

Effects of inhaled corticosteroids on cough in awake guinea pigs with experimental allergic rhinitis--the first experience.

Allergic rhinitis is a common cause of chronic cough. Topical corticosteroids are regarded as the most effective first-time treatment in allergic rhinitis. In this study we evaluated the cough sensitivity during the early and late allergic responses in guinea pigs with experimental allergic rhinitis. Another aim of the study was to follow up the effect of inhaled beclomethasone dipropionate on the cough in guinea pigs with allergic rhinitis. 31 guinea pigs were sensitized with ovalbumin (OA). Animals were intranasally challenged with OA (experiment) or saline (control) in 7-day intervals for 9 weeks. Cough was induced by inhalation of citric acid aerosols in gradually increasing concentrations for 30 s and was evaluated 1 h after the 8(th) nasal challenge (NCH) and 17 h after the 9(th) NCH. Cough was significantly increased only during an early allergic response, 1 h after repeated NCH [18 (14-23) vs. 8 (3-10); P<0.001]. Five experimental animals were inhaling aerosol of beclomethasone dipropionate seven days between the 8(th) and the 9(th) NCH and cough was evaluated 1 h after the 9(th) NCH. Inhaled corticosteroids significantly inhibited the enhanced allergic rhinitis related cough [4 (1-9) vs.19 (9-37) vs. 6 (3-9); P<0.05].