Nasal Obstruction: Overview of Pathophysiology and Presentation of a Clinically Relevant Preoperative Plan for Rhino(Septo)plasty.

Impairment of nasal breathing is a highly prevalent and bothersome symptom that affects daily functioning and/or sleep quality. Those surgeons dealing with patients seeking rhinoplasty need to carefully analyze the preoperative nasal breathing capacity and predict the positive or even negative impact of rhino(septo)plasty on nasal breathing. Given the lack of correlation between the subjective feeling of suboptimal nasal breathing and the objective measurements of nasal flow and nasal resistance, a critical and mainly clinical evaluation of all anatomical, mucosal, and sensory mechanisms involved in nasal obstruction is mandatory. Indeed, thermo-, mechano-, and chemosensory receptors on the nasal mucosa, airflow, and respiratory dynamics might all contribute to the overall perception of nasal breathing capacity. In this review, we provide an overview of the factors determining suboptimal nasal breathing including different diagnostic and experimental tests that can be performed to evaluate nasal flow and nasal resistance and current limitations in our understanding of the problem of nasal breathing in an individual patient. An algorithm for the preoperative or diagnostic workup for nasal obstruction is included that might be useful as a guide for clinicians dealing with patients seeking nose surgery.

[The state of mucociliary transport of the mucous membrane of the inferior turbinates in children after various types of vasotomy]. / Sostoyanie mukotsiliarnogo transporta slizistoi obolochki nizhnikh nosovykh rakovin u detei posle razlichnykh vidov vazotomii.

The article presents the results of a study that included 127 children aged 8 to 17 years with a diagnosis of turbinate hypertrophy. The children are divided into three groups depending on the chosen vasotomy method. The methods of vasotomy were determined, after which there was a faster restoration of mucociliary clearance of the mucous membrane of the lower nasal concha.

The effect of autosomal dominant polycystic kidney disease on mucociliary clearance.

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a renal disease with genetic transmisson. Mutations in the PKD1 and PKD2 genes, which encode integral membrane proteins of the cilia of primary renal tubule epithelial cells, are seen in ADPKD. The aim of this study was to evaluate the sinonasal epithelium, which is epithelium with cilia, by measuring the nasal mucociliary clearance time, and to investigate the effect of ADPKD on nasal mucociliary clearance. METHODS: The study included 34 patients, selected from patients followed up in the Nephrology Clinic, and 34 age and gender-matched control group subjects. The nasal mucociliary clearance time (NMCT) was measured with the saccharin test. RESULTS: The mean age of the study subjects was 47.15 ± 14.16 years in the patient group and 47.65 ± 13.85 years in the control group. The eGFR rate was determined as mean 72.06 ± 34.26 mL/min in the patient group and 99.79 ± 17.22 mL/min in the control group (p < 0.001). The NMCT was determined to be statistically significantly longer in the patient group (903.6 ± 487.8 s) than in the control group (580 ± 259 s) (p = 0.006). CONCLUSIONS: The study results showed that the NMCT was statistically significantly longer in patients with ADPKD compared to the control group, but in the linear regression analysis results, no correlation was determined between eGFR and NMCT.

Objective measurement and patient-reported evaluation of the nasal airway: Is correlation dependent on symptoms or on nasal airflow?

BACKGROUND: Evidence has shown that the sensation of nasal breathing is related to variations in nasal mucosa temperature produced by airflow. An appropriate nasal airflow is necessary for changing mucosal temperature. Therefore, the correlation between objective measurements of nasal airflow and patient-reported evaluation of nasal breathing should be dependent on the level of nasal airflow. OBJECTIVES: To find if the correlation between patient-reported assessment of nasal breathing and objective measurement of nasal airflow is dependent on the severity of symptoms of nasal obstruction or on the level of nasal airflow. METHODS: The airway of 79 patients was evaluated using NOSE score and peak nasal inspiratory flow (PNIF). Three subgroups were created based on NOSE and three subgroups were created based on PNIF level to find if correlation was dependent on nasal symptoms or airflow. RESULTS: The mean value of PNIF for the 79 patients was 92.6 L/min (SD 28.1 L/min). The mean NOSE score was 48.4 (SD 24.4). The correlation between PNIF and NOSE was statistically significant (P = .03), but with a weak association between the two variables (r = -.248). Evaluation of correlation based on symptoms demonstrated a weak or very weak association in each subgroup (r = -.250, r = -.007, r = -.104). Evaluation of correlation based on nasal airflow demonstrated a very weak association for the subgroups with middle-level and high PNIF values (r = -.190, r = -.014), but a moderate association for the subgroup with low PNIF values (r = -.404). CONCLUSIONS: This study demonstrated a weak correlation between NOSE scores and PNIF values in patients non-selected according to symptoms of nasal obstruction or to airflow. It demonstrated that patients with symptoms of nasal obstruction have different levels of nasal airflow and that low nasal airflow prevents the sensation of good nasal breathing. Therefore, patients with symptoms of nasal obstruction may require improving nasal airflow to improve nasal breathing sensation.

Chloride Conductance, Nasal Potential Difference and Cystic Fibrosis Pathophysiology.

PURPOSE: Cystic fibrosis (CF) is a multisystem genetic disease caused by dysfunction of the epithelial anionic channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Decreased mucociliary clearance because of thickened mucus is part of the pulmonary disease pathophysiology. It is controversial if the thickened airway surface liquid (ASL) is caused by the deficient chloride secretion and excessive sodium (through ENaC) and water hyperabsorption from the periciliar fluid or by the lack of bicarbonate secretion with relative acidification of the ASL. Correlations between the magnitude of in vivo chloride conductance with phenotypic characteristics and CF genotype can help to elucidate these mechanisms and direct to new treatments. METHODS: Nasal potential difference was measured in 28 CF patients (age from 0.3 to 28 year) and correlated with pulmonary function, pancreatic phenotype, pulmonary colonization and genotype severity. RESULTS: The CFTR-chloride conductance was better in older patients (r = 0.40; P = 0.03), in patients with better pulmonary function (r = 0.48; P = 0.01), and was associated with genotype severity. Higher chloride diffusion in the presence of a favorable chemical gradient was associated with Pseudomonas aeruginosa negativity (P < 0.05). More negative NPDmax was associated with pancreatic insufficiency (P < 0.01) as well with genotype severity, but not with the pulmonary function. CONCLUSIONS: The anion permeability through CFTR, mainly chloride, but bicarbonate as well, is the most critical factor in CF airway pathophysiology. Treatments primarily directed to correct CFTR function and/or airway acidity are clearly a priority.

The effect of premature ovarian insufficiency on nasal mucociliary clearance time.

Premature ovarian insufficiency (POI) is a global health concern for women and affects several systems, such as cardiovascular system, autoimmune disease, and psychological status. The aim of this study was to investigate the effect of POI on nasal mucociliary clearance time via saccharin test by comparing postmenopausal women and healthy controls. Thirty-five (35) patients with POI, 35 healthy postmenopausal women and 35 healthy controls were recruited in this study. All study participants underwent measurements of nasal mucociliary clearance time via saccharine test. When women with POI and postmenopausal women compared with the controls, nasal mucociliary clearance time was longer in both women with POI and postmenopausal women. When women with POI were compared with postmenopausal women, the nasal mucociliary clearance time was not difference between two groups. There was a significant prolonged nasal mucociliary clearance time in the women with POI and postmenopausal women. Lower serum estradiol levels in women with POI as well as postmenopausal women had an adverse effect of nasal mucociliary clearance time.

Expression, Distribution and Role of Aquaporins in Various Rhinologic Conditions.

Aquaporins (AQPs) are water-specific membrane channel proteins that regulate cellular and organismal water homeostasis. The nose, an organ with important respiratory and olfactory functions, is the first organ exposed to external stimuli. Nose-related topics such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS) have been the subject of extensive research. These studies have reported that mechanisms that drive the development of multiple inflammatory diseases that occur in the nose and contribute to the process of olfactory recognition of compounds entering the nasal cavity involve the action of water channels such as AQPs. In this review, we provide a comprehensive overview of the relationship between AQPs and rhinologic conditions, focusing on the current state of knowledge and mechanisms that link AQPs and rhinologic conditions. Key conclusions include the following: (1) Various AQPs are expressed in both nasal mucosa and olfactory mucosa; (2) the expression of AQPs in these tissues is different in inflammatory diseases such as AR or CRS, as compared with that in normal tissues; (3) the expression of AQPs in CRS differs depending on the presence or absence of nasal polyps; and (4) the expression of AQPs in tissues associated with olfaction is different from that in the respiratory epithelium.

Evaluation of nasal mucociliary clearance time in patients with Vitamin-D deficiency.

OBJECTIVES: The main purpose of the current study was to investigate nasal mucociliary clearance time (NMC) in patients with Vitamin-D deficiency. METHODS: A total of 55 patients with Vitamin-D deficiency and 32 controls were evaluated. NMC time was measured with subjective saccharine test and compared between study and control groups. In addition, NMC time was re-evaluated after Vitamin-D replacement protocol in patients with Vitamin-D deficiency. RESULTS: The mean 25(HO)Vitamin-D levels were 14.32 ± 4.23 ng/mL (7-24.6) and 29.38 ± 7.05 ng/mL (25-53.8) in study and control groups, respectively (p < 0.001). The mean NMC time was 11.15 ± 3.05 (6.3-17.6) and 8.40 ± 2.33 (6-13.2) in study and control groups, respectively (p < 0.001). The mean 25(HO)Vitamin-D level after the replacement protocol was 33.38 ± 10.03 and the mean NMC time was 9.56 ± 2.54 (p < 0.001). CONCLUSION: The mean NMC time was significantly increased in patients with Vitamin-D deficiency which can be corrected after Vitamin-D replacement protocols. The prolonged mucociliary clearance might be one of the pathophysiologic pathways at increased upper respiratory tract infections, and sinonasal and ear infections in patients with Vitamin-D deficiency.

Etiopathogenesis of Primary Acquired Nasolacrimal Duct Obstruction: What We Know and What We Need to Know.

PURPOSE: To provide a systematic review of the literature on the etiopathogenesis of primary acquired nasolacrimal duct obstruction (PANDO). METHODS: The authors performed a PubMed search of all articles published in English with specific reference to etiopathogenesis of PANDO or associations of PANDO. Data captured include demographics, study techniques, hypothesis, presumed or confirmed interpretations with regards to pathogenesis, mechanisms, or pathways. Specific emphasis was laid on addressing the lacunae and potential directions for future research. RESULTS: Numerous factors are believed to contribute to the etiopathogenesis of PANDO. The basic pathogenesis involves inflammation, vascular congestion, mucosal edema, fibrosis, obstruction, and stasis. Bony nasolacrimal duct diameter does not appear to play a significant role. There is no convincing data to substantiate nose as the site of disease origin and nasal factors appear to be comorbidities. Hormonal mechanisms are more evidence-based but can only partly explain the pathogenesis. Vascular theories are based on the behavior of perilacrimal cavernous bodies, their autonomic control, and additional structural changes in the helical patterns of connective tissue fiber arrangements. Repeated vascular malfunction leading to structural epithelial and subepithelial changes currently appears to be the most evidence-based and accepted theory. Tear proteomics holds a promise in decoding the etiopathogenesis of PANDO, at least in part. CONCLUSIONS: The etiopathogenesis of PANDO appears to be multifactorial. Hormonal microenvironments, vascular factors, and tear proteomics are promising candidates for further work. There is a need for focused work by Clinician-Scientists and the answers can have far reaching clinical implications.

Repeatability of nasal allergen challenge results: Further validation of the allergic rhinitis clinical investigator collaborative protocols.

BACKGROUND: Nasal allergen challenge (NAC) models have been used to study allergic rhinitis and new therapies. Symptoms and biological samples can be evaluated at time points after allergen exposure. OBJECTIVE: To verify protocol repeatability and adequate interval between allergen exposures. METHODS: Ten ragweed allergic participants were exposed to incrementally increasing dosages of ragweed allergen intranasally until they achieved a total nasal symptom score (TNSS) of 8 of 12 and a peak nasal inspiratory flow (PNIF) of 50% reduction or more from baseline. Three weeks later, participants were challenged with a cumulative dose equal to the sum of all the allergen doses received at screening. TNSS and PNIF were recorded at regular intervals, including a 24-hour assessment. A subsequent visit was conducted after a further 3 weeks. Nasal secretion samples were collected for cytokine and eosinophil quantification. RESULTS: Nine participants completed all visits. TNSS and PNIF responses followed previous patterns, with an initial peak at 30 minutes followed by a gradual decline. Most participants reported similar patterns at both NAC visits, although some did not demonstrate the same phenotype at both visits. Some experienced a secondary symptom increase 24 hours after NAC. Eosinophil and cytokine sections followed a similar pattern at both NAC visits. CONCLUSION: NAC is an adequate method for modeling AR in humans, demonstrating appropriate repeatability of symptoms, nasal mucosal eosinophil, and cytokines. The 24-hour time point, previously not studied in our model, may be beneficial in evaluation of long-acting medications. This three-week interval NAC model will be beneficial for studies in which before and after treatment comparisons are desired.

Effects of oral isotretinoin on normal and wounded nasal mucosa: an experimental study.

BACKGROUND: We aimed to investigate the effect of systemic isotretinoin therapy on normal and wounded nasal septal mucosa histopathologically in an experimental rabbit model. METHODS: Circular mucosal defect with a 7 mm diameter was made in the left septum of 12 New Zealand white rabbits. The rabbits were divided into two groups (six rabbits in each group) oral isotretinoin was given with olive oil at the operation day to the first group. The control group was only oil given group. The harvested septum mucosas were divided into four groups (1-wounded-drug given side, 2-unwounded and drug-given side, 3-wounded-control and 4-unwounded-control side). The diameter of the defect, mucosal thickness, epithelial thickness, ciliated cell level, goblet cell level and inflammation were evaluated every week for 4 weeks. RESULTS: At both wounded and normal side, thinning of normal respiratory ciliated epithelium was observed in the postoperative period. In study group at the wounded side; mean mucosal thickness was measured 139.66 µ (± 26.24), and in the control group, mean mucosal thickness was 238.33 µ (± 39.7) at the wounded side. (p < 0.001). The difference between the groups in thickness of normal septal mucosa was also statistically significant (p = 0.016) [190 µ (± 14.6) and 256.66 µ (± 44.66)]. The average cilia level was observed 1.16 in the wounded study group, while the average level was 2.33 in the wounded control group (p = 0.012). Average score measurements of the regenerated mucosa suggested that isotretinoin-given wounded animals have reduced goblet cell recovery, compared to the control both on the regenerated and unwounded mucosas (p = 0.007, p = 0.002, respectively). Inflammation was significantly higher in the wounded isotretinoin group (p = 0.018). CONCLUSION: Oral isotretinoin has negative effects on epithelial and ciliary regeneration, significantly reduces mucosal thickness and goblet cell counts of the normal and regenerated mucosa, causes severe inflammation and significant reactive changes.

[The distribution of interleukins and cytokines in the mucous membranes of the nose and the nasopharynx in the patients presenting with the post-nasal drip syndrome]. / Raspredelenie interleikinov i tsitokinov v slizistoi obolochke nosa i nosoglotki pri izolirovannom sindrome postnazal'nogo zatekaniia.

The objective of the present study was to elucidate the distribution of interleukins and cytokines in the mucous membranes of the nose and the nasopharynx in the patients presenting with the post-nasal drip syndrome. The study included 20 patients with this pathological condition and 20 volunteers who comprised the control group. The samples of the mucous membranes of the nose and the nasopharynx were examined with the use of the immunohistochemical methods to identify the protein gene product 9.5, interleukin-6, interleukin-10, the tumour necrosis factor-alpha, nuclear factor-kB, and beta-defensin. It was shown that the post-nasal drip syndrome is characterized by the enhanced content of the protein gene product 9.5, interleukin-6, interleukin-10, the tumour necrosis factor-alpha, nuclear factor-kB, and beta-defensin in the mucous membranes of the nose and the nasopharynx.

Volumetric changes of grafted volumes and the Schneiderian membrane after transcrestal and lateral sinus floor elevation procedures: A clinical, pilot study.

AIM: To investigate the influence of various surgical techniques for sinus augmentation on the volumetric changes of graft, membrane and the post-operative discomfort. MATERIALS AND METHODS: Eighteen patients in need of bilateral sinus floor elevation (SFE) were assigned to lateral SFE, transcrestal SFE and intralift procedures. CBCT images taken at baseline, 1 week and 6 weeks were analysed for volumetric changes in graft and Schneiderian membrane. Questionnaires were used to analyse post-op discomfort. RESULTS: The overall average graft volume obtained after 1 week was 1.87 cm3 (range 0.12-4.72 cm3 ). Volumes decreased after 6 weeks to an overall mean volume of 1.33 cm3 (range 0.10-4.29 cm3 - average decrease of 27.6%). After 6 weeks, the amount of graft volume decreased in every treatment option, ranging from -23.13% for the tSFE, over -24.55% for the lSFE, to -33.71% for the IL. Although all treatment options correspond in an increase in Schneiderian membrane volume, no statistically significant correlation between this increase and loss of graft volume could be obtained for all treatments (p = 0.97). CONCLUSION: All SFE techniques provided sufficient graft volume for implant treatment. All techniques provoke a partially transient swelling of the Schneiderian membrane. All techniques resulted in a decrease in graft volume after 6 weeks; however, no significant differences were obtained between treatments. Furthermore, no statistical significant correlation between the post-operative swelling of the Schneiderian membrane and reduction in graft volume at 6 weeks could be obtained.

Nasal nitric oxide improved by continuous positive airway pressure therapy for upper airway inflammation in obstructive sleep apnea.

PURPOSE: In this report, we examined the association between obstructive sleep apnea (OSA) and upper and lower airway inflammation based on nitric oxide (NO) measurements. METHODS: Study subjects included 51 consecutive participants. Sleep-disordered breathing was evaluated by a type 3 portable monitor and quantified by respiratory disturbance index (RDI). Airway inflammation was noninvasively analyzed by the measurement of nasally and orally exhaled NO; nasal value was presented as nasally exhaled NO minus orally exhaled NO. In 15 patients prescribed nasal continuous positive airway pressure (nCPAP) therapy, exhaled NO was re-evaluated in 10.7 ± 6.3 months after nCPAP therapy. RESULTS: Nasal NO was significantly higher in patients with severe OSA (RDI ≥ 30/h) than those with non-OSA (RDI < 10/h) (76.9 ± 26.0 ppb vs. 47.9 ± 22.0 ppb, respectively, p = 0.016) and correlated with RDI (rho = 0.36, p = 0.0099), whereas orally exhaled NO did not differ between non-OSA and OSA patients and was not correlated with RDI. In 15 patients, nasal NO after nCPAP therapy was significantly decreased than that before nCPAP therapy (81.9 ± 31.2 ppb vs. 53.7 ± 27.2 ppb, respectively, p = 0.0046); in 11 patients having good compliance to nCPAP therapy (nCPAP use >4 h per night on more than 70% of nights), this association was more remarkable. CONCLUSIONS: In OSA, upper but not lower airway inflammation can be increased by repetitive collapse of the upper airway. Future studies are required to determine the role of nasal NO in OSA.

Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation.

Solitary chemosensory cells (SCCs) of the nasal cavity are specialized epithelial chemosensors that respond to irritants through the canonical taste transduction cascade involving Gα-gustducin and transient receptor potential melastatin 5. When stimulated, SCCs trigger peptidergic nociceptive (or pain) nerve fibers, causing an alteration of the respiratory rate indicative of trigeminal activation. Direct chemical excitation of trigeminal pain fibers by capsaicin evokes neurogenic inflammation in the surrounding epithelium. In the current study, we test whether activation of nasal SCCs can trigger similar local inflammatory responses, specifically mast cell degranulation and plasma leakage. The prototypical bitter compound, denatonium, a well-established activator of SCCs, caused significant inflammatory responses in WT mice but not mice with a genetic deletion of elements of the canonical taste transduction cascade, showing that activation of taste signaling components is sufficient to trigger local inflammation. Chemical ablation of peptidergic trigeminal fibers prevented the SCC-induced nasal inflammation, indicating that SCCs evoke inflammation only by neural activity and not by release of local inflammatory mediators. Additionally, blocking nicotinic, but not muscarinic, acetylcholine receptors prevents SCC-mediated neurogenic inflammation for both denatonium and the bacterial signaling molecule 3-oxo-C12-homoserine lactone, showing the necessity for cholinergic transmission. Finally, we show that the neurokinin 1 receptor for substance P is required for SCC-mediated inflammation, suggesting that release of substance P from nerve fibers triggers the inflammatory events. Taken together, these results show that SCCs use cholinergic neurotransmission to trigger peptidergic trigeminal nociceptors, which link SCCs to the neurogenic inflammatory pathway.

The effects of the stem cell on ciliary regeneration of injured rabbit sinonasal epithelium.

Defects in mucosal healing after sinonasal surgery cause infection, scar formation causing obstruction, relapse of the disease within a shorter period and revision surgery. The present study aimed to create a functional ciliated epithelium using a stem cell and stem cell sheet of adipose tissue origin and to show such regeneration ultra-structurally on experimentally injured rabbit nasal epithelium. This was an experimental animal study and basic research. A total of 18 white New Zealand rabbits were divided into three groups. The medial wall of the maxillary sinus of the subjects was peeled off bilaterally. No additional procedure was applied to the subjects in Group 1. In Group 2, adipose tissue-derived mesenchymal stem cell was implanted on the wound edges of the subjects. In Group 3, a stem cell sheet of three layers was laid onto the defect area. All subjects were killed after 3 weeks. The presence of the stem cell stained with bromo-deoxyuridine was assessed with a light microscope, whereas cilia density, ciliated orientation and cilia structure were evaluated with a scanning electron microscope. Ciliary densities in Group 2 and Group 3 were statistically superior compared to the control group (p < 0.001, p = 0.007). Cilia morphology in Group 2 and Group 3 was also better than the control group (p < 0.01, p = 0.048). Ciliary orientation in Group 2 was scored highest (p < 0.01). The ratio of BrDu-stained cells was observed to be 27% in Group 3 and 8% in Group 2. Sub-epithelial recovery was observed to be better in Group 3. Adipose tissue-derived mesenchymal stem cell increased the healing of the injured maxillary sinus mucosa of the rabbits in terms of cilia presence, density and morphology regardless of the implementation technique. Level of evidence NA.

[Pregnancy Rhinitis - an Update]. / Update Schwangerschaftsrhinitis.

Pregnancy rhinitis (PR), a common condition in pregnant women, is defined as long-lasting nasal congestion due to mucosal swelling and increased secretion without any signs of infection, allergy or tumor, starting at any time during pregnancy and disappearing within 2 weeks of delivery. Smoking and a sensitization to house dust mites are known risk factors. While a definitive pathophysiological concept for PR does not exist, hormonal influences are discussed. We present a stepwise therapeutic strategy for PR and an overview to the latest literature.

[Medically-induced rhinitis]. / Medikamentoznyi rinit.

This paper summarizes the currently accepted concepts of the pathogenetic mechanisms underlying the morphological and functional changes in intranasal mucosa of the patients having a long history of the application of the long-acting topical vasoconstrictor agents. The author presents the data illustrating the effectiveness of various methods for the pharmacotherapeutic treatment of medically-induced rhinitis.

Evaluation of nasal mucociliary activity in patients with chronic renal failure.

The ability of respiratory mucosal surfaces to eliminate foreign particles and pathogens and to keep mucosal surfaces moist and fresh depends on mucociliary activity. Chronic renal failure (CRF) is an irreversible medical condition that may result in important extrarenal systemic consequences, such as cardiovascular, metabolic, and respiratory system abnormalities. Although there are studies describing nasal manifestations of CRF, data are lacking concerning the effects of the condition on nasal mucosa. The goal of the current study was to evaluate nasal mucociliary clearance (NMC) time in patients with CRF. This prospective cohort study conducted in a tertiary referral center included 32 non-diabetic end-stage CRF patients and 30 control individuals. The control group consisted of voluntary participants who had been referred to our clinic for symptoms other than rhinological diseases. The mean NMC times in CRF patients and control individuals were 12.51 ± 3.74 min (range 7-22 min) and 8.97 ± 1.83 min (range 6-13 min), respectively. The mean NMC time in patients with CRF was significantly longer than that in control individuals (p < 0.001). Clinicians must keep in mind that NMC time in CRF patients is prolonged and must follow-up these patients more closely for sinonasal and middle ear infections.