A Case Study of Vitamin D Supplementation Therapy and Acute Respiratory Tract Infection.

BACKGROUND: Low serum concentrations of 25-hydroxyvitamin D correlate with higher susceptibility to acute respiratory tract infections (ARTIs). The case study presented here aims at sheding light on the correlation between vitamin D levels, the vitamin D supplement dose, and the incidence of ARTIs. CASE REPORT: A 23-year-old female patient with a vitamin D insufficiency was able to successfully increase her vitamin D levels from 45.60 nmol/l to 85.91 nmol/l (reference ranges 75-200 nmol/l) through the use of supplements. However, it was surprising to observe a decrease in vitamin D levels even though the patient continued taking supplements. Further examination indicated that the patient was experiencing common symptoms of an acute respiratory tract infection (ARTI). This case highlights the intricate connection between ARTIs and vitamin D intake. CONCLUSION: This case study clearly demonstrates the intricate connection between vitamin D levels, supplement treatment, and ARTIs. The observed decrease in vitamin D levels during the course of supplementation, while the patient was suffering from an ARTI, suggests that respiratory infections may affect vitamin D metabolism.

Effect of fermented milk on upper respiratory tract infection in adults who lived in the haze area of Northern China: a randomized clinical trial.

CONTEXT: Upper respiratory tract infection (URTI) is the most common illness in humans. Fermented milk containing probiotics can mitigate URTI symptoms. OBJECTIVE: This study tests the effect of fermented milk (Qingrun), a yogurt supplemented with Bifidobacterium animalis subsp. lactis Bl-04, on adults with URTIs who live in a haze-covered area in a randomized clinical trial. MATERIALS AND METHODS: A total of 136 subjects were enrolled in the study at the baseline and randomized to consume either control yogurt or Qingrun yogurt (250 g) once daily for 12 weeks. The duration and severity of URTI were evaluated by the Wisconsin Upper Respiratory Symptom Survey-24. Blood and faecal samples were collected at the baseline and post-intervention, to determine the changes of immune biomarkers. RESULTS: Qingrun yogurt significantly reduced the incidence of the common cold (OR, 0.38; 95% CI, 0.17-0.81; p = 0.013) and influenza-like illness (OR, 0.32; 95% CI, 0.11-0.97; p = 0.045). Compared to the control yogurt, Qingrun yogurt significantly reduced the duration (1.23 ± 2.73 vs. 4.78 ± 5.09 d) and severity score (3.58 ± 7.12 vs. 11.37 ± 11.73) of URTI. In addition, the post-intervention levels of interferon-γ (139.49 ± 59.49 vs. 113.45 ± 65.12 pg/mL) and secretory immunoglobulin A (529.19 ± 91.70 vs. 388.88 ± 53.83 mg/dL) significantly increased in the Qingrun group, compared with those in the control group. CONCLUSIONS: Qingrun yogurt showed a protective effect against URTI in adults, suggesting that the use of yogurt with probiotics could be a promising dietary supplement for mitigating URTI.

The effect of vitamin D supplementation on acute respiratory tract infection in older Australian adults: an analysis of data from the D-Health Trial.

BACKGROUND: Observational studies have linked vitamin D deficiency with acute respiratory tract infection, but results from randomised controlled trials are heterogeneous. We analysed data from the D-Health Trial to determine whether supplementing older Australian adults, recruited from the general population, with monthly doses of vitamin D reduced the risk, duration, and severity of acute respiratory tract infections. METHODS: We used data from the D-Health Trial, a randomised, double-blind, placebo-controlled trial of monthly vitamin D supplementation, for which acute respiratory infection was a pre-specified trial outcome. Participants were supplemented and followed for up to 5 years. The trial was set within the Australian general population, using the Commonwealth Electoral Roll as the sampling frame, but also allowing some volunteers to participate. Participants were men and women aged 60 to 79 years (with volunteers up to age 84 years). Participants were randomly assigned to receive either vitamin D or placebo (1:1) using computer-generated permuted block randomisation, which was stratified by age, sex, and state. This was an automated process and the assignment list was not visible to study staff or investigators. Active and placebo gel capsules, identical in appearance to ensure masking, were labelled A and B and the code was not available to study staff or investigators. Participants were asked to report occurrence of acute respiratory symptoms over the previous month via annual surveys, and a subset of participants completed 8-week respiratory symptom diaries in winter. As part of our process to maintain blinding, a random sample of participants was selected for analysis of survey data and a separate sample selected for analysis of diary data. Blood samples were obtained from a random sample of participants (about 450 per group per year) and serum 25-hydroxy vitamin D (25[OH]D) concentrations were measured to monitor adherence. We used regression models to estimate odds ratios (OR), rate ratios, and rate differences. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763. FINDINGS: Between Jan 13, 2014, and May 26, 2015, 421 207 invitations were sent, 40 824 people were interested in participating, and 21 315 participants were recruited and randomised. Of the 16 000 participants selected for potential analysis of survey data, 15 373 were included in the analysis; 295 in the vitamin D group and 332 in the placebo group who were missing data for all five annual surveys were excluded from the analysis. Of the 3800 selected for potential analysis of diary data, 3070 were invited to complete the diaries because 730 had already withdrawn. 2598 people were included in the analysis; 218 people in the vitamin D group and 254 in the placebo group were missing data and were therefore excluded from the analysis. In blood samples collected from randomly sampled participants throughout the trial, the mean serum 25(OH)D concentration was 114·8 (SD 30·3) nmol/L in the vitamin D group and 77·5 (25·2) nmol/L in the placebo group. Vitamin D supplementation did not reduce the risk of acute respiratory tract infection (survey OR 0·98, 95% CI 0·93 to 1·02; diary OR 0·98, 0·83 to 1·15). Analyses of diary data showed reductions in the overall duration of symptoms and of severe symptoms, but these were small and unlikely to be clinically significant. INTERPRETATION: Monthly bolus doses of 60 000 IU of vitamin D did not reduce the overall risk of acute respiratory tract infection, but could slightly reduce the duration of symptoms in the general population. These findings suggest that routine vitamin D supplementation of a population that is largely vitamin D replete is unlikely to have a clinically relevant effect on acute respiratory tract infection. FUNDING: National Health and Medical Research Council.

Beneficial therapeutic effects of vitamin C on recurrent respiratory tract infections in children: preliminary data.

BACKGROUND: The aim of this study was to demonstrate whether supplementation of vitamin C has a beneficial effect in the prevention of recurrent respiratory tract infections (RTIs) in children. Moreover, we evaluate the main risk factors that predispose to the development of this disease. METHODS: Sixty children have been enrolled in the study and randomized into two groups: the control group (G1 N.=33) and the group at risk of recurrent RTIs (G2 N.=27). To G2 group was administered every day 100% orange juice with the content of vitamin C 70 mg. RESULTS: Significant reduction in the incidence rate of RTIs (episodes pre-treatment: 182-6.75 episodes/child, after-treatment: 71-2.62 episodes/child, P<0.05), were observed in G2 group. CONCLUSIONS: The administration of vitamin C had a beneficial effect in our group of children with recurrent RTIs, reducing the number of infective episodes.

A standardized polyphenol mixture extracted from poplar-type propolis for remission of symptoms of uncomplicated upper respiratory tract infection (URTI): A monocentric, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: The most common symptoms of mild upper respiratory tract infections (URTIs) are sore throat, muffled dysphonia, and swelling and redness of the throat, which result from the inflammation process following acute bacterial or viral infection. HYPOTHESIS/PURPOSE: As propolis is a natural resinous substance traditionally used to maintain oral cavity and upper respiratory tract health due to its antimicrobial and anti-inflammatory properties, the aim of this study is to evaluate the efficacy of an oral spray based on poplar-type propolis extract with a known and standardized polyphenol content, on the remission of the symptoms associated with mild uncomplicated URTIs. STUDY DESIGN: A monocentric, randomized, double-blind, placebo-controlled clinical trial was performed. METHODS: This study was conducted in 122 healthy adults who had perceived mild upper respiratory tract infections. Participants, randomly assigned to receive either propolis oral spray (N = 58) or placebo (N = 64), underwent four visits (baseline = t0, after 3 days = t1 and after 5 days = t2 and after a follow-up of 15 days = t3) in an outpatient setting. Propolis oral spray total polyphenol content was 15 mg/ml. The dosage was 2-4 sprays three times/day (corresponding to 12-24 mg of polyphenols/day), for five days. The duration of the study was 8 weeks. RESULTS: After 3 days of treatment, 83% of subjects treated with propolis oral spray had remission of symptoms, while 72% of subjects in the placebo group had at least one remaining symptom. After five days, all subjects had recovered from all symptoms. This means that resolution from mild uncomplicated URTIs took place two days earlier, instead of taking place in five days as recorded in the control group. There was no relationship between the ingestion of propolis oral spray or placebo and adverse reactions. CONCLUSION: Propolis oral spray can be used to improve both bacterial and viral uncomplicated URTI symptoms in a smaller number of days without the use of pharmacological treatment, leading to a prompt symptom resolution.

Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19.

There are limited proven therapies for COVID-19. Vitamin C's antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6-24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients' vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.

Vitamin D to prevent COVID-19: recommendations for the design of clinical trials.

The coronavirus disease 2019 (COVID-19) pandemic has focused attention on the potential role of vitamin D supplementation to prevent COVID-19. In this issue, Merzon and colleagues report epidemiologic data on the vitamin D status of 7807 individuals and their risk of developing COVID-19. In multivariable analyses, low vitamin D status was associated with increased risk of both COVID-19 infection and hospitalization. The authors call for clinical trials of vitamin D supplementation. In this Commentary, we discuss some of the challenges of vitamin D research and provide recommendations for the design of randomized controlled trials of vitamin D supplementation to prevent COVID-19.

Microbial contamination of coffee during postharvest on farm processing: A concern for the respiratory health of production workers.

Coffee workers respiratory health problems, found to be associated with dust exposure in the coffee factories, but the content of the dust is not well known. A cross-sectional survey was conducted to assess the microbial contamination of coffee in dry and wet coffee process, from four farms in two regions of Ethiopia. A total of 36 samples of coffee were collected for laboratory investigation. The microbial load in the dry process ranged from 6.9 × 102 to 7.2 × 105 colony forming units (CFU)/mL while the microbial load in wet process ranged from 2.5 × 102 to 4.6 × 105 CFU/mL. The results indicate the presence of gram negative bacteria in dried and stored beans from both the wet and dry process. During further coffee processing possible release of endotoxin from coffee contaminated by gram negative bacteria might affect coffee workers respiratory health. Further studies are required to assess the relation between bacterial contamination of coffee and endotoxin level in coffee factories.

The association between vitamin D status and infectious diseases of the respiratory system in infancy and childhood.

PURPOSE: Respiratory tract infections (RTIs) are a major cause of illness worldwide and the most common cause of hospitalization for pneumonia and bronchiolitis. These two diseases are the leading causes of morbidity and mortality among children under 5 years of age. Vitamin D is believed to have immunomodulatory effects on the innate and adaptive immune systems by modulating the expression of antimicrobial peptides, like cathelicidin, in response to both viral and bacterial stimuli. The aim of this review is to summarize the more recently published data with regard to potential associations of 25-hydroxyvitamin D [25(OH)D] with infectious respiratory tract diseases of childhood and the possible health benefits from vitamin D supplementation. METHODS: The literature search was conducted by using the PubMed, Scopus, and Google Scholar databases, with the following keywords: vitamin D, respiratory tract infection, tuberculosis, influenza, infancy, and childhood. RESULTS: Several studies have identified links between inadequate 25(OH)D concentrations and the development of upper or lower respiratory tract infections in infants and young children. Some of them also suggest that intervention with vitamin D supplements could decrease both child morbidity and mortality from such causes. CONCLUSIONS: Most studies agree in that decreased vitamin D concentrations are prevalent among most infants and children with RTIs. Also, normal to high-serum 25(OH)D appears to have some beneficial influence on the incidence and severity of some, but not all, types of these infections. However, studies with vitamin D supplementation revealed conflicting results as to whether supplementation may be of benefit, and at what doses.

Childhood iron deficiency anemia leads to recurrent respiratory tract infections and gastroenteritis.

Anemia affects approximately 30% of children all over the world. Acute respiratory tract infections (ARTI), urinary tract infections (UTI) and gastroenteritis (GE) are common infectious entities in children. Here, we assessed the association between anemia and development of recurrent ARTI, UTI, and GE in children. This was a case-control study in hospitalized 2-5 years old children in Professorial Pediatric Unit at Teaching Hospital Anuradhapura, Sri Lanka. An 18-month follow up was done to assess the risk factors for the development of recurrent ARTI, GE, UTI, and control presented without infections. Further, 6-month follow up done after 3-month iron supplementation to assess the occurrence of recurrences. Blood Hb concentration was measured using Drabking's reagent. Logistic regression was used to find the risk factors for the development of recurrences. In ARTI, 121/165 (73.3%), GE, 88/124 (71%), UTI 46/96 (47.9%) and control 40/100 (40%) were having anemia. Initial ARTI group, recurrent ARTI was 24 (14.5%, p = 0.03); initial GE group: recurrent GE was 14 (11.3%, p = 0.03), recurrent ARTI was 11 (8.9%, p = 0.04); initial UTI group, development of; recurrent UTI was 8 (8.3%, p = 0.04); control, recurrent ARTI was 11 (11%, p = 0.03). Following 3-month iron supplementation reduction of recurrences was significant: initial ARTI recurrent ARTI in 90%, recurrent GE in 77.7%; initial GE recurrent GE in 83.3%, recurrent ARTI in 80%; initial UTI recurrent ARTI in 71.4% and control recurrent ARTI in 88.8%. Iron deficiency is a major type of anemia and anemic children are more prone to develop recurrent ARTI and GE. Once iron deficiency being corrected the rate of recurrent ARTI and GE was reduced. This would be a boost for policy developers to implement strategies at the community level to prevent iron deficiency in children to reduce ARTI and GE recurrences.

High-throughput screening identifies candidate drugs for the treatment of recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a benign neoplasm of the larynx caused mainly by human papillomavirus type 6 or 11 and its standard treatment involves repeated surgical debulking of the laryngeal tumors. However, significant morbidity and occasional mortality due to multiple recurrences occur. Conditional reprogramming (CR) was used to establish a HPV-6 positive culture from an RRP patient, named GUMC-403. High-throughput screening was performed at the National Center for Advanced Technology (NCATS) to identify potential drugs to treat this rare but morbid disease. GUMC-403 cells were screened against the NPC library of >2800 approved drugs and the MIPE library of >1900 investigational drugs to identify new uses for FDA-approved drugs or drugs that have undergone significant research and development. From the two libraries, we identified a total of 13 drugs that induced significant cytotoxicity in RRP cells at IC50 values that were clinically achievable. We validated the efficacy of the drugs in vitro using CR 2D and 3D models and further refined our list of drugs to panobinostat, dinaciclib and forskolin as potential therapies for RRP patients.

Paediatric and adult bronchiectasis: Monitoring, cross-infection, role of multidisciplinary teams and self-management plans.

Bronchiectasis is a chronic lung disease associated with structurally abnormal bronchi, clinically manifested by a persistent wet/productive cough, airway infections and recurrent exacerbations. Early identification and treatment of acute exacerbations is an integral part of monitoring and annual review, in both adults and children, to minimize further damage due to infection and inflammation. Common modalities used to monitor disease progression include clinical signs and symptoms, frequency of exacerbations and/or number of hospital admissions, lung function (forced expiratory volume in 1 s (FEV1 )% predicted), imaging (radiological severity of disease) and sputum microbiology (chronic infection with Pseudomonas aeruginosa). There is good evidence that these monitoring tools can be used to accurately assess severity of disease and predict prognosis in terms of mortality and future hospitalization. Other tools that are currently used in research settings such as health-related quality of life (QoL) questionnaires, magnetic resonance imaging and lung clearance index can be burdensome and require additional expertise or resource, which limits their use in clinical practice. Studies have demonstrated that cross-infection, especially with P. aeruginosa between patients with bronchiectasis is possible but infrequent. This should not limit participation of patients in group activities such as pulmonary rehabilitation, and simple infection control measures should be carried out to limit the risk of cross-transmission. A multidisciplinary approach to care which includes respiratory physicians, chest physiotherapists, nurse specialists and other allied health professionals are vital in providing holistic care. Patient education and personalized self-management plans are also important despite limited evidence it improves QoL or frequency of exacerbations.

Effect of oral nutritional supplementation on growth and recurrent upper respiratory tract infections in picky eating children at nutritional risk: a randomized, controlled trial.

Objectives To evaluate the effect of oral nutritional supplementation (ONS) plus dietary counselling (DC) (intervention) versus DC alone (control) on growth and upper respiratory tract infection (URTI) in nutritionally at-risk, picky eating children in India. Methods We performed a 90-day, prospective, randomized, controlled trial. A total of 255 children aged 24-72 months with a weight-for-age z-score ≥-2 and <-1, picky eating behaviour, and acute URTI were randomized to the control (n = 128) or intervention group (n = 127). The outcomes included the change in weight-for-age z-score from days 1 to 90 and the URTI incidence. Results The mean age was 44.0 ± 14.3 months. The intervention group showed a significantly greater increase in mean weight-for-age and body mass index-for-age z-scores compared with the control group from day 10 onwards. Higher energy intake in the intervention group was observed at all follow-up visits, except for day 10. The incidence of URTI in the control group was 2.01 times higher than that in the intervention group, controlling for confounding factors. Conclusions ONS plus DC is effective for improving weight and reducing the incidence of URTI in nutritionally at-risk, picky eating children with an acute URTI episode.

Short-course antimicrobial therapy for paediatric respiratory infections (SAFER): study protocol for a randomized controlled trial.

BACKGROUND: Community-acquired pneumonia (CAP) is commonly diagnosed in children. The Infectious Disease Society of America guidelines recommend 10 days of high-dose amoxicillin for the treatment of non-severe CAP but 5-day "short course" therapy may be just as effective. Randomized trials in adults have already demonstrated non-inferiority of 5-day short-course treatment for adults hospitalized with severe CAP and for adults with mild CAP treated as outpatients. Minimizing exposure to antimicrobials is desirable to avoid harms including diarrhoea, rashes, severe allergic reactions, increased circulating antimicrobial resistance, and microbiome disruption. METHODS: The objective of this multicentre, randomized, non-inferiority, controlled trial is to investigate whether 5 days of high-dose amoxicillin is associated with lower rates of clinical cure 14-21 days later as compared to 10 days of high-dose amoxicillin, the reference standard. Recruitment and enrolment will occur in the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. All children in the study will receive 5 days of amoxicillin after which point they will receive either 5 days of a different formulation of amoxicillin or a placebo. Assuming a clinical failure rate of 5% in the reference arm, a non-inferiority margin of 7.5%, one-sided alpha set at 0.025 and power of 0.80, 270 participants will be required. Participants from a previous feasibility study (n = 60) will be rolled over into the current study. We will be performing multiplex respiratory virus molecular testing, quantification of nasopharyngeal pneumococcal genomic loads, salivary inflammatory marker testing, and faecal microbiome profiling on participants. DISCUSSION: This is a pragmatic study seeking to provide high-quality evidence for front-line physicians evaluating children presenting with mild CAP in North American emergency departments in the post-13-valent pneumococcal, conjugate vaccine era. High-quality evidence supporting the non-inferiority of short-course therapy for non-severe paediatric CAP should be generated prior to making changes to established guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02380352 . Registered on 2 March 2015.

Analysis of specialized nursing on respiratory functions in thoracotomy patients.

To analyze the nursing effect on the respiratory function of thoracotomy patients, sixty thoracotomy hospitalized patients were studied. The subjects were divided into a normal group (A) and an observation group (B). The patients in group A received routine nursing only, while those in group B received chest physiotherapy as well as routine nursing. Afterwards, the respiratory function indicators of the two groups were compared and a data analysis was performed. The results showed that the partial pressure of oxygen (PO2) value of the patients in group B was greater than that of the patients in group A while the partial pressure of carbon dioxide (PCO2) value in group B was smaller than that in group A, and there was a significant difference between the two groups (p less than 0.05). The vital capacity under normal circumstances and forced breathing of group B were greater than that of group A and the difference was statistically significant (p less than 0.05). The incidence of complications (atelectasis, respiratory infections, pleural effusion) was statistically significant between the two groups (p less than 0.05). The degree of autonomic respiratory dysfunction in group B was lower than that in group A, and there was a significant difference (p less than 0.05), suggesting that the respiratory function in patients receiving chest physiotherapy improved significantly.

Novel antibiotic combinations proposed for treatment of Burkholderia cepacia complex infections.

Effective strategies to manage Burkholderia cepacia complex (Bcc) infections in cystic fibrosis (CF) patients are lacking. We tested combinations of clinically available antibiotics and show that moxifloxacin-ceftazidime could inhibit 16 Bcc clinical isolates at physiologically achievable concentrations. Adding low dose of colistin improved the efficacy of the combo, especially at conditions mimicking CF respiratory secretions.

Novel variant of common variable immunodeficiency.

A 57-year-old woman with frequent respiratory infections was initially diagnosed with IgG subclass deficiency based on low levels of IgG subclasses 2 and 3. Three years later, she progressed to having IgA deficiency as well. With a normal total IgG level, she does not meet criteria for common variable immunodeficiency (CVID). This may represent a variant of CVID. This also highlights the importance of immunoglobulin subclass estimation in patients where immunodeficiency is suspected clinically. She is being treated with rotational antibiotics the first 10 days of every month, monthly intravenous immunoglobulin (IVIG) infusion and osteopathic manipulation one to two times per month. On this regimen, although she has had several viral respiratory infections, she has avoided further hospitalisation for more than 1 year.