Safety and efficacy of P2X3 receptor antagonist for the treatment of refractory or unexplained chronic cough: A systematic review and meta-analysis of 11 randomized controlled trials.

BACKGROUND AND OBJECTIVES: Chronic refractory cough is a challenging condition that requires a thorough evaluation and management approach. P2X3 receptors that are ATP-dependent play an important part in nerve fiber sensitization and pathological pain pathways. We conducted this systematic review and meta-analysis to determine the long-term safety and efficacy of P2X3 receptor antagonist drugs in chronic cough. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase to identify all relevant published studies through January 15, 2023 that assessed P2X3 antagonists in chronic cough. The protocol was registered in the PROSPERO database with ID: CRD42023422408. Efficacy outcomes were awake (daytime) cough frequency, night cough frequency, 24-h cough frequency, Cough Severity Diary, and total Leicester Cough Questionnaire score. We used the random-effect model to pool the data using RStudio and CMA software. RESULTS: A total of 11 randomized controlled trials comprising 1350 patients receiving a p2x3 antagonist compared to the placebo group were included in this meta-analysis. A significant decrease in 24-h cough frequency (MD = -4.99, 95% CI [-7.15 to -2.82], P < 0.01), awake (daytime) cough frequency (MD = -7.18, 95% CI [-9.98 to 4.37], P < 0.01), and total Leicester Cough Questionnaire score (MD = 1.74, 95% CI [1.02 to 2.46], P < 0.01) exhibited between the P2X3 antagonist and placebo groups. The frequency of the night cough showed an insignificant difference between the two groups. According to the safety, drug-related adverse events, dysgeusia, hypogeusia, and ageusia significantly increased between the P2X3 antagonist and placebo groups. CONCLUSION: P2X3 receptor antagonists are promising drugs for treating chronic cough by significantly reducing the frequency, severity, and quality. Some potential side effects may include drug-related adverse events such as hypogeusia, ageusia, and dysgeusia.

Use of Favipiravir for the Treatment of Coronavirus Disease 2019 in the Setting of Hospitel.

Objective: In a setting with a limited capacity for hospitalization, "hospitels" have been developed by using hotels as extension healthcare facilities for patients with mild illness. This study examined the clinical evidence of patients with coronavirus disease 2019 (COVID-19) who were treated with favipiravir, the main medication for treating COVID-19, in the hospitel setting in Thailand. Methods: We retrospectively collected demographic and clinical information, medication treatment, and outcome data for all patients who received favipiravir for COVID-19 during admission to a hospitel from April 27, 2021, to July 2, 2021. Risk factors for adults who could not complete treatment in a hospitel and who required hospitel transfer were analyzed. Results: In total, 421 patients were included in the study. Most patients (94.5%) received favipiravir to treat COVID-19 pneumonia. Adjunctive corticosteroids were prescribed to 42.3% of patients. Concerning the treatment outcome, 83.6% of patients completed treatment at a hospitel, and only two deaths occurred. No serious adverse drug reactions were observed. On multivariate analysis, age (odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.10, P=0.002), dyspnea (OR = 2.84; 95% CI = 1.25-6.44, P=0.013), loss of taste (OR = 107.63; 95% CI = 1.24-9337.39, P=0.040), corticosteroid use (OR = 12.56; 95% CI = 3.65-43.18, P < 0.001), and an extended duration of favipiravir use (OR = 16.91; 95% CI = 7.29-39.24, P < 0.001) were associated with a higher risk of hospitel transfer. Conclusions: Low rates of hospitel transfer and mortality were observed in mild-to-moderate COVID-19 patients treated with favipiravir at hospitel. Caution might be required in elderly patients, patients with dyspnea or a loss of taste, and patients receiving a 10-day course of favipiravir or adjunctive corticosteroids because these patients might require further management in the hospitel.

Therapeutic supplementation with zinc in the management of COVID-19-related diarrhea and ageusia/dysgeusia: mechanisms and clues for a personalized dosage regimen.

Zinc supplementation is indicated for diarrhea and taste disorders, which are both features of COVID-19 . Nevertheless, this strategy has not been tested for the treatment of these secondary complications in the current pandemic. Through an updated review, a practical appraisal was considered as a means of providing a medical nexus of therapeutic zinc regimens as an adjunct in the management of COVID-19-related diarrhea and ageusia/dysgeusia. While diarrhea and taste disorders are consequences of COVID-19, zinc supplementation is useful for non-COVID-19 patients with these clinical problems. The overwhelming evidence for supplementing with zinc in diarrhea and pneumonia is associated with the treatment of children, while for taste disorders the use of supplementing with zinc is more examined in adults. Whereas COVID-19 is more prevalent in adults, precautions should be exercised not to translate the zinc dosage used for children with diarrhea and taste disorders into the current pandemic. Therapeutic doses of zinc used for adults (∼50-150 mg/day of elemental zinc) could be included in the treatment strategies for COVID-19, but this proposal should be examined through randomized studies.

Potential pharmacologic treatments for COVID-19 smell and taste loss: A comprehensive review.

The acute loss of taste and smell following COVID-19 are hallmark symptoms that affect 20-85% of patients. However, the pathophysiology and potential treatments of COVID-19 smell and taste loss are not fully understood. We searched the literature to review the potential pathologic pathways and treatment options for COVID-19 smell and taste loss. The interaction of novel coronavirus with ACE-2 receptors expressed on sustentacular cells and taste buds results in direct damage to the olfactory and gustatory systems. Also, the invasion of the virus to the olfactory neurons and consequent local inflammation are other proposed mechanisms. Therefore, COVID-19 patients with smell or taste loss may benefit from neuroprotective, anti-inflammatory, or depolarizing agents. Based on the current evidence, phosphodiesterase inhibitors, insulin, and corticosteroids can be promising for the management of COVID-19 smell and taste loss. This review provided crucial information for treating COVID-19-related smell and/or taste loss, urging to perform large clinical trials to find optimum treatment options.

Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia.

The year 2020 became the year of the outbreak of coronavirus, SARS-CoV-2, which escalated into a worldwide pandemic and continued into 2021. One of the unique symptoms of the SARS-CoV-2 disease, COVID-19, is the loss of chemical senses, i.e., smell and taste. Smell training is one of the methods used in facilitating recovery of the olfactory sense, and it uses essential oils of lemon, rose, clove, and eucalyptus. These essential oils were not selected based on their chemical constituents. Although scientific studies have shown that they improve recovery, there may be better combinations for facilitating recovery. Many phytochemicals have bioactive properties with anti-inflammatory and anti-viral effects. In this review, we describe the chemical compounds with anti- inflammatory and anti-viral effects, and we list the plants that contain these chemical compounds. We expand the review from terpenes to the less volatile flavonoids in order to propose a combination of essential oils and diets that can be used to develop a new taste training method, as there has been no taste training so far. Finally, we discuss the possible use of these in clinical settings.

A 44-Year-Old Hispanic Man with Loss of Taste and Bilateral Facial Weakness Diagnosed with Guillain-Barré Syndrome and Bell's Palsy Associated with SARS-CoV-2 Infection Treated with Intravenous Immunoglobulin.

BACKGROUND This case report is of a patient who presented with loss of taste and facial weakness and was diagnosed with Guillain-Barre syndrome (GBS) and Bell's palsy, associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. GBS is a neurological emergency defined as acute inflammatory demyelinating polyneuropathy. The patient responded to intravenous immunoglobulin (IVIG) treatment. CASE REPORT We present the case of a 44-year-old Hispanic man who came for evaluation of bilateral facial weakness and lack of taste sensation. He had lower motor neuron facial weakness. His head computed tomography and brain magnetic resonance imaging scans did not show any pathological abnormalities. He tested positive for SARS-CoV-2 by a nasopharyngeal swab reverse transcription polymerase chain reaction (RT-PCR) test. Cerebrospinal fluid (CSF) analysis via lumbar puncture revealed elevated protein levels, no leukocytes, and a negative Gram stain. The CSF RT-PCR test for SARS-CoV-2 was negative. PCR tests of the CSF for other viral infections were negative. A diagnosis of GBS was made, and he was treated successfully with IVIG. After the fourth dose of IVIG, the patient was able to close his eyes, frown, show his teeth, and smile. CONCLUSIONS Our case is rare because the patient did not present with lower extremity weakness, but only with bilateral Bell's palsy. Physicians should be aware of GBS because it is a neurological emergency for which COVID-19 can be a risk factor. Early diagnosis and treatment of GBS can prevent neurological disability.

Application of umami taste stimulation to remedy hypogeusia based on reflex salivation.

Enjoying taste should be one of the greatest pleasures in human life. However, aging is sometimes associated with decreased taste sensitivity, also known as hypogeusia. The loss of taste not only affects quality of life, but can also cause weight loss and health problems in the elderly. Our recent study has shown that 37% of test subjects over 65 years of age exhibited hypogeusia. Further, whole saliva secretion, including minor salivary secretion, was significantly decreased in elderly patients with gustatory impairment, but was normal in all elderly subjects with normal taste thresholds. These data indicate that hyposalivation is closely related to hypogeusia. Moreover, clinical studies have shown that treatment of hyposalivation diminishes hypogeusia, indicating that salivation is essential to maintain normal taste function. However, many medications for relief of dry mouth, such as parasympathomimetic (cholinomimetic) drugs, have serious adverse effects. Palpitation, sweating, nausea, diarrhea and dizziness have all been observed in elderly patients taking parasympathomimetic drugs. To circumvent this problem, glutamate, which produces umami taste, was demonstrated to increase salivary secretion and thereby improve hypogeusia by enhancing the gustatory-salivary reflex. Our data suggests that umami is an effective tool for the relief of hypogeusia without the side effects of parasympathomimetic drugs.

Effects of zinc supplementation on serum zinc concentration and ratio of apo/holo-activities of angiotensin converting enzyme in patients with taste impairment.

OBJECTIVE: The aim of the present study was to evaluate the effects of zinc supplementation on hypogeusia, serum zinc concentration and the ratio of apo/holo-activities of angiotensin converting enzyme (ACE ratio) in patients with taste impairment. ACE ratio was used as an index of zinc nutritional status. METHODS: Forty patients complaining of taste impairment were divided into two groups: zinc deficiency taste impairment (n=12) and idiopathic taste impairment (n=28). Patients with zincemia values of less than 63 microg/dl with no history of other disorder or medication known to cause dysgeusia were diagnosed as zinc deficiency group, while those with the same condition and values more than 64 microg/dl were considered to belong to the idiopathic group. Patients orally received 150 mg of polaprezinc containing 33 mg of zinc every day. Subjective symptom was scored according to visual analogue scale (VAS). RESULTS: Zinc supplementation improved hypogeusia in both idiopathic and zinc deficiency groups. The mean improvements of VAS were 3.02+/-3.03 in the idiopathic group and 3.13+/-2.53 in the zinc deficiency group. Thus, there were no significant differences in idiopathic and zinc deficiency groups. Significant correlations were found between the improvement of VAS score and the ACE ratio after zinc supplementation in both idiopathic and zinc deficiency groups. On the contrary, significant correlations were not found between the improvement of VAS score and the zinc concentration in the serum after zinc supplementation in both groups. CONCLUSION: The results of the present study indicated that zinc deficiency is a predominant factor underlying taste impairment and ACE ratio may be a predictor of the prognosis for taste impairment after zinc supplementation, in addition to a more sensitive indicator of zinc nutrition than zinc concentration in the serum.

Brain gamma-aminobutyric acid levels are decreased in patients with phantageusia and phantosmia demonstrated by magnetic resonance spectroscopy.

BACKGROUND: Olfactory and gustatory hallucinations (phantosmias and phantageusias, respectively) are sensory distortions that commonly follow losses of olfactory and gustatory acuity (hyposmia and hypogeusia, respectively). The biochemical basis of these hallucinations is unclear. Functional magnetic resonance imaging has been used previously to demonstrate widespread and robust central nervous system (CNS) activation to memories of these sensory distortions in patients with these symptoms. In this study, possible CNS mechanisms responsible for these distortions were evaluated using magnetic resonance spectroscopy, because this technique has been used to measure various CNS metabolites in patients with neurologic disorders. METHODS: Forty-seven subjects were studied: 28 normal volunteers (13 men and 15 women) and 19 patients (8 men and 11 women) with persistent oral global phantageusia and/or birhinal phantosmia studied before any treatment. Four patients (1 man and 3 women) were studied before and after pharmacologic treatment that reduced the severity of their sensory distortions. All subjects were studied in a Signa 1.5-T magnetic resonance scanner with a quadrature head coil using a modified standard 2-dimensional J-point resolved excitation in the steady state (PRESS) sequence by which gamma-aminobutyric acid (GABA), glutamic acid, choline, N-acetylaspartate, and creatine (Cre) were measured in various CNS regions. Results were expressed using Cre as a denominator to determine ratios for each measurement. Differences were defined between normal subjects and patients before treatment and in patients before and after successful pharmacologic treatment. RESULTS: Before treatment, GABA levels in several CNS regions were lower in patients than in normal volunteers and were the only biochemical changes found; significantly lowered GABA levels were found in the cingulate, right and left insula, and left amygdala. No differences between patients and normal volunteers were found in any of the metabolites in the posterior occipital region. After treatment that inhibited sensory distortions, CNS GABA levels increased in the cingulate, insula, and amygdala but significantly only in the left insula and in the right and left amygdala. After this successful treatment, no change in any biochemical parameter was found in the posterior occipital region. CONCLUSIONS: These results indicate that decreased brain GABA levels can serve as biochemical markers of phantageusia and/or phantosmia in patients with these distortions and are the first biochemical changes in the CNS that reflect these sensory changes. After successful treatment of these distortions, CNS GABA levels increased to levels at or near normal, consistent with functional remission of these symptoms. These results substantiate a role for CNS GABA in the generation and inhibition of these sensory hallucinations. Although the underlying biochemical mechanism(s) for the generation of these decreased GABA levels are complex, because similar types of sensory hallucinations occur as auras or prodromata of epileptic seizure and migraine activity, these results suggest that there may be common biochemical changes among these disorders.

[A case of polaprezinc-induced pneumonitis].

A 77-year-old man referred to our hospital three months ago presented with dyspnea on effort and chest radiograph abnormalities. Chest computed tomography showed consolidation and irregular thickening of the peribronchovascular interstitium. Bronchoalveolar lavage fluids showed increases in the percentage of lymphocytes and a decrease of the CD4/8 ratio. Transbronchial lung biopsy specimens showed signs of organizing pneumonia. The patient had been given polaprezinc for the treatment of hypogeusia six months before. A lymphocyte-stimulating test for polaprezinc was positive, and so our diagnosis was polaprezinc-induced pneumonitis.

[A case of typical Melkersson-Rosenthal syndrome with possible autosomal dominant inheritance].

Here we presented a case of 40-year-old woman who suffered from bilateral facial palsy and headache. She had allegedly had an episode of facial palsy, and facial edema at her age of 14 years. Physical examination revealed swelling of the lips, upward disturbance of the left eye, hypogeusia, the fissured tongue, and bilateral facial palsy. Oral administration of prednisolone 20 mg/day yielded gradual but complete improvement of the facial palsy and hypogeusia within two weeks. Careful analysis of family history disclosed that four members had oro-facio-cervical edema and three had the fissured tongue. A diagnosis of Melkersson-Rosenthal syndrome with possible autosomal dominant inheritance was made based on the clinical findings and familial aggregation of the incomplete form of this syndrome.