Mid-treatment Fluorodeoxyglucose Positron Emission Tomography in Human Papillomavirus-related Oropharyngeal Squamous Cell Carcinoma Treated with Primary Radiotherapy: Nodal Metabolic Response Rate can Predict Treatment Outcomes.

AIMS: To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). MATERIALS AND METHODS: This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan-Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. RESULTS: There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). CONCLUSION: The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

A systematic review and meta-analysis of treatment-related toxicities of curative and palliative radiation therapy in non-small cell lung cancer.

Treatment-related toxicity is an important component in non-small cell lung cancer (NSCLC) management decision-making. Our aim was to evaluate and compare the toxicity rates of curative and palliative radiotherapy with and without chemotherapy. This meta-analysis provides better quantitative estimates of the toxicities compared to individual trials. A systematic review of randomised trials with > 50 unresectable NSCLC patients, treated with curative or palliative conventional radiotherapy (RT) with or without chemotherapy. Data was extracted for oesophagitis, pneumonitis, cardiac events, pulmonary fibrosis, myelopathy and neutropenia by any grade, grade ≥ 3 and treatment-related deaths. Mantel-Haenszel fixed-effect method was used to obtain pooled risk ratio. Forty-nine trials with 8609 evaluable patients were included. There was significantly less grade ≥ 3 acute oesophagitis (6.4 vs 22.2%, p < 0.0001) and any grade oesophagitis (70.4 vs 79.0%, p = 0.04) for sequential CRT compared to concurrent CRT, with no difference in pneumonitis (grade ≥ 3 or any grade), neutropenia (grade ≥ 3), cardiac events (grade ≥ 3) or treatment-related deaths. Although the rate of toxicity increased with intensification of treatment with RT, the only significant difference between treatment regimens was the rate of oesophagitis between the use of concurrent and sequential CRT. This can aid clinicians in radiotherapy decision making for NSCLC.

[The value of serum abnormal prothrombin in clinical application of hepatocellular carcinoma].

Objective: To examine the value of serum protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) detection in the early diagnosis and surveillance of hepatocellular carcinoma (HCC). Methods: The clinical data of 215 patients with HCC admitted to Department of Hepatobiliary-Pancreatic Surgery of China-Japan Union Hospital of Jilin University from October 2017 to May 2018 were analyzed retrospectively. There were 172 males and 43 females, aged of (59.0±9.3) years old (range 34 to 86 years old). In addition, there were 85 non HCC patients were enrolled in the control group, 42 males and 43 females, aged (54.2±11.3) years old (range 22 to 80 years old). The blood sample of 3 ml was drawn from the elbow vein at 6∶00 am on the next day of admission, and then was kept in low temperature away from light, and sent for PIVKA-Ⅱ detection on the same day. The positive value of AFP was ≥20 µg/L and PIVKA-Ⅱ was ≥32 AU/L. The data were analyzed statistically by χ(2) test, t test or rank sum test. The correlation between AFP, PIVKA-Ⅱ and tumor maximum diameter was analyzed by linear regression. Results: The sensitivity of PIVKA-Ⅱ detection only for the diagnosis of HCC in all stages was significantly higher than AFP or equivalent to AFP, the overall sensitivity of PIVKA-Ⅱ and AFP was 85.1% and 52.1%, respectively. But the specificity of PIVKA-Ⅱ was lower than that of AFP, they were 78.8% and 96.5%, respectively. In particularly, in the earlier stage of HCC (Ⅰa) , the sensitivity of PIVAK-Ⅱ to HCC was 64.5%, while the AFP was only 26.3%. Combined detection of PIVKA-Ⅱ and AFP significantly improved the diagnostic rate of HCC to 88.4%, and the specificity to 76.5%. Moreover, there was a positive correlation between PIVKA-Ⅱ level and the maximum tumor diameter (r(2)=0.587, P<0.05), but there was no correlation between the AFP level and the maximum tumor diameter (r(2)=0.296, P>0.05). The positive rate of PIVKA-Ⅱ in the diagnosis of HCC with vascular invasion was also significantly higher than that of AFP (P<0.01) . Conclusions: PIVKA-Ⅱ can be used as a serological marker for HCC screening and diagnosis. In particular, PIVKA-Ⅱ detection was significantly sensitive than AFP in the earlier stage of HCC. Combined detection of PIVKA-Ⅱ and AFP can effectively improve the diagnostic rate of HCC in all stages. The significant elevation of PIVKA-Ⅱ is also helpful to determine the tumor aggressiveness, vascular invasion and prognosis of HCC patients.

[Change of esophageal length measured on computed tomography after corrective osteotomy for cervicothoracic kyphosis in patients with ankylosing spondylitis and its clinical significance].

Objective: To investigate the change of esophageal length measured on computed tomography after C(7) pedicle subtraction osteotomy (PSO) for cervicothoracic kyphosis in ankylosing spondylitis (AS) patients and its clinical significance. Methods: Eight male AS patients with cervicothoracic kyphosis, who underwent PSO at C(7) level from December 2014 to November 2018 at Nanjing Drum Tower Hospital, were retrospectively reviewed. The mean age was (35±7) years (range, 26-49 years). The cervicothoracic kyphosis, C(2)-T(1) sagittal vertical axis (SVA) and angle of fusion levels (AFL) were measured on lateral cervical radiographs and chin-brow vertical angle (CBVA) was measured on clinical photographs preoperatively and postoperatively. Anterior height of the osteotomized vertebra (AHOV) and esophageal length from the lower endplate of C(6) to the inferior endplate of the lower instrumented vertebrae were measured on sagittal plane of reconstructed computed tomography preoperatively and postoperatively. Oswestry Disability Index (ODI), Neck Disability Index (NDI) and Numerical Rating Scale (NRS) were collected to evaluate the clinical outcomes. Results: The average follow-up duration was (15±9) months (range, 3-51 months). The average correction of cervicothoracic kyphosis, C(2)-T(1)SVA, AFL and CBVA was 35.9°±7.3°, (44.7±11.6) mm, 32.0°±4.8° and 38.1°±11.5°, respectively. The average reduction of AHOV was (5.6±1.6) mm. ODI was improved from 17±14 preoperatively to 13±10 at the final follow-up. The NDI before operation and at the final follow-up was 18±15 and 10±6, respectively. The preoperative NRS was 4.8±2.4, and it decreased to 1.0±1.2 at the final follow-up. The change of esophageal length showed significant correlation with the improvement of cervicothoracic kyphosis, C(2)-T(1)SVA, AFL and CBVA(r=0.84, 0.83, 0.83, 0.73, all P<0.05). Conclusions: The operation of C(7)PSO increases esophageal length after cervicothoracic kyphosis in AS patients. The esophageal elongation is closely related with changes of parameters measured on radiographs and clinical photographs. Spine surgeons should be aware of the potential risk of esophagus-related complications caused by esophagus lengthening after C(7)PSO.

Circulating human papillomavirus DNA detection in Barrett's dysplasia and esophageal adenocarcinoma.

There is evidence to suggest that human papillomaviruses (HPV) are associated with Barrett's dysplasia and esophageal adenocarcinoma. In other HPV-linked cancers such as cervical and oropharyngeal cancer, circulating HPV DNA is a potential biomarker to assist in tumor diagnosis and management. This study aimed to determine whether circulating HPV DNA was detectable in patients with Barrett's dysplasia and esophageal adenocarcinoma, and if so, whether there is any correlation with esophageal tissue HPV status. Plasma from 138 patients representing esophageal adenocarcinoma (N = 41), Barrett's dysplasia (N = 48) and hospital controls (N = 49) were analyzed for the presence of circulating HPV DNA using droplet-digital PCR targeting the E7 gene of HPV types 16 and 18. Circulating HPV DNA was detected in 11/138 (8.0%) study subjects including 1/49 (2.0%) hospital controls, 4/48 (8.3%) Barrett's dysplasia patients, and 6/41 (14.6%) esophageal adenocarcinoma patients. Detection of circulating HPV DNA was higher in patients with HPV-positive esophageal tissue (6/35, 17.1%) compared to those with HPV-negative specimens (5/103; 4.9%) (OR = 4.06; 95% CI 1.15-14.25; P = 0.020). The highest rates of detection occurred in esophageal adenocarcinoma patients, particularly those with invasive tumors that had breached the esophageal submucosa, had regional lymph node involvement or metastatic disease. Circulating HPV DNA was detectable in a subset of Barrett's dysplasia and esophageal adenocarcinoma patients. Detection was associated with tissue HPV positivity and possibly disease severity.

ICOS/ICOSL upregulation mediates inflammatory response and endothelial dysfunction in type 2 diabetes mellitus.

OBJECTIVE: ICOS/ICOSL plays a crucial part in various disease-mediated immune responses. However, the exact role of ICOS/ICOSL in type 2 diabetes mellitus (T2DM) development remains unexplored. This study aims to investigate the role of ICOS/ICOSL in the pathogenesis of T2DM. MATERIALS AND METHODS: Human peripheral blood T-lymphocytes (CD3) and umbilical vein endothelial cells (HUVECs) were treated with high-glucose (HG) or advanced glycation end products (AGEs). A portion of CD3 cells was co-cultured with HUVECs and treated with different mediums or anti-ICOS mAbs. The ICOS/ICOSL and caspase-3 protein expression was measured by Western blotting. ELISA (enzyme-linked immunosorbent assay), MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and NOx production assays were respectively used to detect cytokines level, cell viability and the production of NOx. RESULTS: HG and AGEs significantly upregulated ICOS/ICOSL expressions in T cells and HUVECs. T cell contact with HUVECs secreted more IFN-γ, IL-4, and IL-10 compared to non-contact cells, while cytokines from IL-6-, IL-1ß-, and CM- (the conditioned medium) treated cells did not differ from the control. A significant increase of IL-8 and IL-6 was found in HUVECs under both contact and non-contact conditions vs. control cells. Similar results were also observed in the comparison between CM1- (T cell condition medium) or CM2- (co-culture condition medium) treated cells and control cells. However, CM1 and CM2 treatment significantly inhibited cell viability and increased caspase-3 and NOx production; blocking ICOS/ICOSL remarkably decreased cytokines secretion, enhanced cell viability and reduced caspase-3 and NOx production. CONCLUSIONS: HG and AGEs cause T cell inflammatory response and vascular endothelial dysfunction by upregulating ICOS/ICOSL, which may be one of the possible mechanisms of cardiovascular complications development in T2DM patients.

Human papillomavirus exposure and sexual behavior are significant risk factors for Barrett's dysplasia/esophageal adenocarcinoma.

Given the comparable strains of high-risk human papillomavirus (HPV) present in a subset of Barrett's dysplasia and esophageal adenocarcinoma as in head and neck squamous cell carcinomas and the anatomical proximity of both lesions, we hypothesized that oral sex may increase the risk of Barrett's dysplasia/esophageal adenocarcinoma. Therefore, we compared the sexual behavior of patients with Barrett's dysplasia/esophageal adenocarcinoma and controls (hospital, reflux, and Barrett's metaplasia) to explore a plausible mechanism of viral transmission to the lower esophagus. A hospital-based case-control study involving 36 Barrett's dysplasia/esophageal adenocarcinoma subjects and 55 controls with known HPV DNA status and markers of transcriptional activity i.e p16INK4A and E6/E7 mRNA of the esophageal epithelium was conducted to evaluate differences in sexual history (if any). Barrett's dysplasia/esophageal adenocarcinoma patients were more likely than controls to be positive for HPV DNA (18 of 36, 50% vs. 6/55, 11%, p for trend <0.0001), be male (P = 0.001) and in a relationship (P = 0.02). Viral genotypes identified were HPV 16 (n = 14), 18 (n = 2), 11 (n = 1) and 6 (n = 1). HPV exposure conferred a significantly higher risk for Barrett's dysplasia/esophageal adenocarcinoma as compared with hospital/reflux/Barrett's metaplasia controls (OR = 6.8, 95% CI: 2.1-23.1, adjusted P = 0.002). On univariate analysis, ≥6 lifetime oral sex partners were significantly associated with dysplastic Barrett's esophagus and adenocarcinoma (OR, 4.0; 95% CI: 1.2-13.7, P = 0.046). After adjustment for confounders, HPV exposure and men with ≥2 lifetime sexual partners were at significant risk for Barrett's dysplasia/esophageal adenocarcinoma. If these initial findings can be confirmed in larger studies, it could lead to effective prevention strategies in combating some of the exponential increase in the incidence of esophageal adenocarcinoma in the West.

[Bleeding control of periodontal mechanical therapy for patients taking aspirin].

OBJECTIVE: To investigate the feasibility of periodontal mechanical therapy for chronic periodontitis and coronary heart disease patients with low dose of aspirin. METHODS: Sixty nine chronic periodontitis patients with coronary heart disease were randomly selected as the experimental group (medication group, group A), the control group (withdrawal group, group B) including 20 chronic periodontitis patients with coronary artery disease, stopping the drug for one week and another control group with 50 chronic periodontitis patients (group C). The three groups were examined with pocket probing, and received supragingival scaling, subgingival scaling, and root planning. Local bleeding after operation was observed. In 30 minutes after periodontal mechanical treatment, there was still a need to take some hemostatic measures (containing the oxidized cellulose putting in the periodontal pocket, gauze oppressing, and suturing). Nd:YAG laser was used to stop bleeding 60 minutes after operation. RESULTS: At baseline, there was no significant difference in the three groups, as to the plaque index(PLI), the probing depth (PD), and the attachment loss (AL). The bleeding index (BI)in group A was significantly higher than that in group C (P=0.024), higher than that in group B (P=0.088). The platelet maximum aggregation rate (Agg(max)) was detected in some subjects. The average Agg(max) value group A was 15.2%, which was much greater than that in group B (60.7%) and group C (62.5%). The three groups were all safe in the treatment of periodontal therapy. There were five cases of active bleeding in group A, one case in group B and one case in group C in 30 minutes after operation. In 60 minutes after operation, there was one case of bleeding actively in group A. Nd:YAG laser was used to stop bleeding successfully. CONCLUSION: The chronic periodontitis and coronary heart disease patients with long-term oral administration of low dose of aspirin can be safely treated with periodontal mechanical treatment, and the effect of local hemostasis is positive without stopping the drug.

Molecular cloning and expression analysis of a novel BCCP subunit gene from Aleurites moluccana.

Aleurites moluccana L. is grown as a roadside tree in southern China and the oil content of its seed is higher than other oil plants, such as Jatropha curcas and Camellia oleifera. A. moluccana is considered a promising energy plant because its seed oil could be used to produce biodiesel and bio-jet fuel. In addition, the bark, leaves, and kernels of A. moluccana have various medical and commercial uses. Here, a novel gene coding the biotin carboxyl carrier protein subunit (BCCP) was cloned from A. moluccana L. using the homology cloning method combined with rapid amplification of cDNA end (RACE) technology. The isolated full-length cDNA sequence (designated AM-accB) was 1188 bp, containing a 795-bp open reading frame coding for 265 amino acids. The deduced amino acid sequence of AM-accB contained a biotinylated domain located between amino acids 190 and 263. A. moluccana BCCP shows high identity at the amino acid level to its homologues in other higher plants, such as Vernicia fordii, J. curcas, and Ricinus communis (86, 77, and 70%, respectively), which all contain conserved domains for ACCase activity. The expression of the AM-accB gene during the middle stage of development and maturation in A. moluccana seeds was higher than that in early and later stages. The expression pattern of the AM-accB gene is very similar to that of the oil accumulation rate.

The effect of diabetes mellitus on costs and length of stay in patients with peripheral arterial disease undergoing vascular surgery.

OBJECTIVE: To determine the impact of diabetes mellitus (DM) and other comorbidities on length of stay (LOS) and costs in patients with peripheral arterial disease (PAD) admitted to a vascular surgical unit. METHODS: A retrospective study was conducted between January 2011 and July 2012 at a tertiary referral hospital in Sydney. Demographic, laboratory, and operative data were obtained from the Australasian Vascular Audit database and hospital diagnostic-related group (DRG) reports. Patients with confirmed PAD with or without DM requiring hospital admission for a diagnosis of claudication, rest pain, ulcer/gangrene, and infection that required lower limb surgical intervention were included. Associations between LOS, surgical procedure, and DRG were explored. RESULTS: Five hundred and sixty-eight admissions (492 patients) were identified: 292 admissions with PAD and 276 admissions with PAD in conjunction with DM (PADDM). Mean LOS for patients with PAD was 10 ± 13.7 days compared with 15 ± 18.2 days for PADDM (p < .01; 95% confidence interval 2.7-8.0). LOS and costs were greatest in patients with PADDM undergoing major amputation (37 ± 13.7 days; US$42,236; p < .01). Analysis of variance indicated that the best predictors of LOS were the presence of DM, bypass surgery, amputation, chronic kidney disease (CKD) stage V, infection, and emergency admission. Over 18 months, the estimated total inpatient costs associated with lower limb intervention for PAD with and without DM amounted to US$7,598,597. People with DM incurred greater inpatient costs, averaging US$1,912 more per episode of admission and a total of US$528,029 over 18 months. CONCLUSION: The impact of diabetes as a comorbid condition in patients with PAD is significant, both clinically and economically. Factors that predict increased LOS in patients with PAD are DM, bypass surgery, amputation, CKD stage V, infection, and emergency admission.

Inhibition of p53 expression by peptide-conjugated phosphorodiamidate morpholino oligomers sensitizes human cancer cells to chemotherapeutic drugs.

The p53 tumor suppressor gene encodes a transcription factor that is commonly mutated in cancer. Tumors arise when premalignant cells are unable to undergo p53-dependent apoptosis, cell cycle arrest or DNA repair. The p53-signaling pathway affects not only tumor development, but also the response of tumors to chemotherapeutic drugs. In this study, we use cell penetrating peptide conjugates of phosphorodiamidate morpholino oligomers (PPMOs) to inhibit p53 expression. We examine the functional properties of endogenous p53 isoforms that are produced upon PPMO-mediated inhibition of p53 translation and splicing, and report that loss of N-terminal or C-terminal sequences interferes with the transcriptional activity of p53. Importantly, we report that PPMO-mediated inhibition of p53 expression sensitizes human cancer cells with wild-type p53 to chemotherapeutic drugs.

Early predictors for developing allergic disease and asthma: examining separate steps in the 'allergic march'.

BACKGROUND: Sensitization and symptoms of allergic disease are strongly correlated, but little is known about the early clinical precursors of the development of allergen sensitization in childhood. The aim of this study was to identify these predictors, and to examine separately the effect of early sensitization on subsequent wheeze, asthma, rhinitis and eczema. METHODS: In the Childhood Asthma Prevention Study, children with a family history of asthma were assessed for allergen sensitization, total serum IgE, wheeze, asthma, eczema and rhinitis at ages 18 months and 5 years. To examine predictors, at 18 months, for subsequent sensitization, children who were non-sensitized at 18 months and had data on sensitization at 5 years were investigated, n=375. To examine the predictors, at age 18 months, of subsequent onset of symptoms, children who did not have wheeze, asthma, eczema or rhinitis at 18 months were followed-up at 5 years, n=177. RESULTS: Among children who were non-sensitized at age 18 months, the presence of eczema [adjusted relative risk (aRR), 1.67, 95% confidence interval (CI) 1.20-2.33], but not wheeze, asthma or rhinitis, was an independent predictor of the onset of sensitization by age 5 years. Among children who were asymptomatic at age 18 months, sensitization to any allergen at 18 months was an independent predictor for the presence of wheeze (aRR 2.41, 95% CI 1.28-4.55), asthma (aRR 4.66, 95% CI 1.88-11.54) and rhinitis (aRR 1.77, 95% CI 1.08-2.90), but not for the development of eczema (aRR 0.78, 95% CI 0.23-2.64) at 5 years. CONCLUSION: In non-sensitized children, eczema, but not wheeze, asthma or rhinitis is a predictor for subsequent development of sensitization. This suggests that early childhood eczema, rather than wheeze and rhinitis, may promote subsequent allergen sensitization and raises the possibility that early management of eczema may reduce the prevalence of sensitization in children.

Two new indole alkaloids from Nauclea officinalis.

Two new indole alkaloids, naucleactonin A and B, along with two known compounds, naucleficine and nauclefidine, were isolated from the bark and wood of Naucleaofficinalis, which has been used as an anti-inflammatory and anti-bacterial agent in folk medicine. Their chemical structures were elucidated by the spectral data, especially 1D and 2D NMR experiments.

The reduction of rhinitis symptoms by nasal filters during natural exposure to ragweed and grass pollen.

BACKGROUND: Prototype nasal filters were developed to collect inhaled pollen. This study evaluated the efficacy of the filters for prevention of rhinitis symptoms during acute outdoor pollen exposure. METHODS: A randomized double-blind design was used. Subjects (n=46) with a history of autumn exacerbation of rhinitis and positive skin test to ragweed, Bermuda and/or Bahia grass wore either active or placebo nasal filters for 2 h in autumn in a park containing these species. Major and Total Symptoms scores were recorded at 0, 30, 60, 90 and 120 min. RESULTS: Subjects wearing active nasal filters had significantly reduced scores, at all time-points compared with placebo group (all P <0.05). Of 14 individual symptoms measured, seven were significantly reduced (number of sneezes, runny nose, itchy nose, sniffles, itchy throat; itchy eyes and watery eyes) and another three showed a trend towards lower severity. The nasal filters also enabled the resolution of existing symptoms. Maximal difference in symptoms was seen immediately after subjects had spent 20 min sitting beside a large patch of ragweed. CONCLUSION: This is the first clinical trial of a nasal filter. The results suggest it has potential for enhancing rhinitis management during acute allergen exposure.

Symptoms of persistent allergic rhinitis during a full calendar year in house dust mite-sensitive subjects.

BACKGROUND: Little is known about the natural course of persistent rhinitis symptoms over a prolonged period. OBJECTIVE: To describe the frequency and severity of nasal symptoms and quality of life (QoL) in house dust mite-sensitive persistent rhinitic subjects and to determine if medication use was related to symptoms. METHODS: Rhinitics and controls were telephoned fortnightly for 1 year to monitor symptoms. QoL was measured every 3 months. RESULTS: Thirty-seven rhinitics and 19 controls completed the study. Total nasal symptom scores (TNSS) were 'high' for 65% (95% CI +/- 6%) of the year in rhinitic subjects. When TNSS increased by 1, the likelihood of nasal medication use increased by 25% (95% CI: 7-46%). General and specific QoL were worse in rhinitic subjects than controls (P < 0.04 and <0.0001). Rhinitics with pollen allergy (n = 21) had seasonal variation in the frequency of high nasal symptom scores (P = 0.02). CONCLUSION: Nasal symptom scores were consistently high in rhinitics, and their QoL was worse than controls, even in general QoL. An increase in nasal symptom score increased the likelihood of nasal medication use. These findings help to characterize the course of persistent rhinitis over a previously unstudied period of 1 year.

Association between nasal and bronchial symptoms in subjects with persistent allergic rhinitis.

BACKGROUND: The association between nasal and bronchial symptoms, and the course of bronchial responsiveness and airway inflammation in house dust mite sensitive persistent rhinitis over a prolonged time period has not been thoroughly explored. OBJECTIVE: To determine if nasal symptoms were associated with bronchial symptoms in persistent rhinitic subjects, and to assess their bronchial responsiveness and airway inflammation in comparison to nonrhinitic, nonatopic controls. The additional impact of pollen sensitivity on the lower airways in rhinitic subjects was also addressed. METHODS: Rhinitics and controls answered telephone symptom questionnaires once every 2 weeks for 1 year. Every 3 months, exhaled nitric oxide (eNO) and bronchial responsiveness to histamine were measured. RESULTS: Thirty-seven rhinitics and 19 controls completed the study. High nasal symptom scores in rhinitic subjects were associated with bronchial symptoms (OR = 1.7, 95% CI 1.2-2.5). Bronchial hyper-responsiveness was present in 32.4% of rhinitic subjects on at least one clinical visit during the year. Pollen allergy caused seasonal variation in eNO (P = 0.03). CONCLUSION: In persistent rhinitic subjects, high nasal symptom scores were associated with bronchial symptoms, and many subjects experienced bronchial hyper-responsiveness during the year. Persistent rhinitic subjects were more at risk than healthy adults of bronchial symptoms and airway inflammation, which are likely risk factors for asthma.

Childhood factors that predict asthma in young adulthood.

Predicting adult asthma, using childhood characteristics, is important for advising on prognosis and, potentially, for secondary prevention. A novel use of multivariate likelihood ratios (LRs) to quantify prognosis is described here. Of 718 subjects of a community-based cohort, 575 (80%) members were recruited at age 8-10 yrs and were re-assessed 15-17 yrs later. At baseline, information about symptoms, spirometry, histamine challenge and skin-prick tests were collected. At follow-up "asthma symptoms" were defined as wheeze, sleep disturbance from asthma or inhaled steroid use within the previous year. LRs were calculated for significant predictors of this outcome. Shinkage factors were applied to yield multivariate LRs. Childhood characteristics that independently predicted asthma symptoms in adulthood were obstructive spirometry (adjusted (adj)LR 2.9, 95% confidence interval (CI) 1.3-6.5), airway hyperresponsiveness (adjLR 2.6, 95% CI 1.8-3.7), atopy (adjLR 2.0, 95% CI 1.5-2.7), recent wheeze (adjLR 1.9, 95% CI 1.5-2.5) and being female (adjLR 1.29, 95% CI 0.8-2.1). Children with all five characteristics had a cumulative LR of 36.9 for asthma symptoms in adulthood. Most adults who had asthma symptoms did not have manifestations of asthma as children. However, the presence of obstructive spirometry, airway hyperresponsiveness and atopy in childhood identifies individuals with increased likelihood of having asthma in adulthood. Cumulative likelihood ratios are more valuable than odds ratios for quantifying risk in individuals and for identifying people with most to gain from preventive interventions.

Risk factors for onset and remission of atopy, wheeze, and airway hyperresponsiveness.

BACKGROUND: Although many children with asthma may have a remission as they grow and other children who did not have asthma may develop asthma in adult life, knowledge about the factors that influence the onset and prognosis of asthma during adolescence and young adulthood is very limited. METHODS: A cohort of 8-10 year old children (n=718) living in Belmont, New South Wales, Australia were surveyed six times at 2 yearly intervals from 1982 to 1992, and then again 5 years later in 1997. From this cohort, 498 subjects had between three and seven assessments and were included in the analysis. Atopy, airway hyperresponsiveness (AHR), and wheeze in the last 12 months were measured at each survey. Late onset, remission, and persistence were defined based on characteristics at the initial survey and the changes in characteristics at the follow up surveys. RESULTS: The proportion of subjects with late onset atopy (13.7%) and wheeze (12.4%) was greater than the proportion with remission of atopy (3.2%) and wheeze (5.6%). Having atopy at age 8-12 years (OR 2.8, 95% CI 1.5 to 5.1) and having a parental history of asthma (OR 2.0, 95% CI 1.02 to 4.13) were significant risk factors for the onset of wheeze. Having AHR at age 8-12 years was a significant risk factor for the persistence of wheeze (OR 4.3, 95% CI 1.3 to 15.0). Female sex (OR 1.9, 95% CI 1.01 to 3.60) was a significant risk factor for late onset AHR whereas male sex (OR 1.9, 95% CI 1.1 to 2.8) was a significant risk factor for late onset atopy. CONCLUSIONS: The onset of AHR is uncommon during adolescence, but the risk of acquiring atopy and recent wheeze for the first time continues during this period. Atopy, particularly present at the age of 8-10 years, predicts the subsequent onset of wheeze.

Clinical importance of Alternaria exposure in children.

The fungus Alternaria is known to be allergenic and is one of the most common fungi worldwide. We investigated the extent to which exposure to Alternaria increases the severity of asthma. We undertook a prospective cohort study in Australia of 399 school children who had positive skin tests to one or more aeroallergens. Airway responsiveness to histamine, wheeze, and bronchodilator use in 1 mo was measured five times between 1997 and 1999. Airway hyperresponsiveness was defined as PD(20)FEV(1) = 3.9 micromol histamine. Airborne concentrations of Alternaria spores were measured throughout the study, and mean daily concentrations over 1 mo ranged from 2.2 to 307.7 spores/m(3) of ambient air. Using generalized estimating equations, we found that airway responsiveness, wheeze, and bronchodilator use increased significantly in association with increased spore concentrations and that the increase in airway responsiveness was greater in children sensitized to Alternaria than in other children (p = 0.01). The odds ratio for airway hyperresponsiveness in children sensitized to Alternaria was 1.26 (95% CI, 1.14 to 1.39) after an increase in mean exposure of 100 spore/m(3)/d over 1 mo. These results suggest that Alternaria allergens contribute to severe asthma in regions where exposure to the fungus is high.

[Study on the inhibition of tea pigments on the adhesion between monocyte and endothelial cells].

In order to study the effects of tea pigments (TP) on the adhesion between monocyte and endothelial cells induced by oxidized low density lipoprotein(Ox-LDL), the fluorescence activated cell sorter (FACS) and the cell ELISA were applied. The results showed that TP could inhibit the adhesion between monocyte and endothelial cells(P < 0.05), and the expression of inter cell adhesion molecule(ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins in a dose dependent manner(P < 0.05). The results suggested that the inhibition of TP on ICAM-1 and VCAM-1 expression was one of the mechanisms of its antiadhesion between monocyte and vascular endothelial cells, as well as that of its antiatherosclerosis.