Effects of triamcinolone acetonide on adult human lung fibroblasts: decrease in proliferation,surface molecule expression and mediator release

BACKGROUND: Lung fibroblasts may have a pivotal role in airway inflammation as they are involved in continuous cycles of mediator secretion, proliferation, activation and cross-talk with recruited inflammatory cells. The role of fibroblasts as intermediate participants in the inflammatory network suggests that they could represent an important target for drugs commonly used in asthma; thus, we investigated the effects of triamcinolone acetonide (TAA) on primary human lung fibroblasts. METHODS: The in vitro activity of increasing concentrations (10(-9) to 10(-7) M) of TAA in fibroblast cultures was evaluated as regards the following parameters: proliferation, extracellular matrix (ECM) release, cytokine/chemokine secretion and surface antigen expression. RESULTS: All concentrations of TAA decreased fetal calf serum (FCS)-induced fibroblast proliferation, whereas in the presence of FCS plus basic fibroblast growth factor TAA was only effective at 10(-8) and 10(-7) M. TAA failed to decrease ECM, whereas at 10(-8) and 10(-7) M it decreased IL-6 and IL-8 secretion to different extents. In the presence of IFN-gamma the drug was able to reduce VCAM-1 expression at all of the tested concentrations; on the other hand, in TGF-beta 1-driven cultures a decrease in CD54 expression was detected with TAA at 10(-8) and 10(-7) M. CONCLUSIONS: TAA acts on some functional properties of human lung fibroblasts that make these cells active participants in the inflammatory network. The ability of TAA to inhibit lung fibroblast proliferation may prevent or even reverse some of the histological changes that characterize airway remodeling in chronic inflammatory diseases; moreover, IL-6, IL-8 and surface molecule decreases by TAA may suggest a direct anti-inflammatory effect of the drug by suppression of resident lung cell function.     

Safety of sublingual immunotherapy with monomeric allergoid in adults: multicenter post-marketing surveillance study

BACKGROUND: Sublingual immunotherapy (SLIT) appears to be acceptably safe in clinical trials, but post-marketing data are needed to provide essential information. This study specifically evaluated the safety of commercial SLIT in adult patients in a post-marketing phase. METHODS: A total of 198 patients (83 male, 115 female, mean age 24.4 years) receiving SLIT for respiratory allergy were followed up for 3 years by a specific questionnaire for side-effects. SLIT (LAIS, Lofarma SpA, Milan, Italy), a monomeric allergoid in tablets, was administered, in association with drug therapy, pre- or pre-coseasonally for pollen and continuously for mites. The average duration was 12-36 months, and the total of doses was about 32 800. Side-effects were grouped as ocular, gastrointestinal, rhinitis, asthma, urticaria, edema of tongue/lips, and anaphylaxis. The severity was graded as low (no need for treatment or dose adjusting, no interference with activities), moderate (interference with activities/need for drugs/SLIT discontinuation), and severe (life-threatening/hospitalization/emergency care). RESULTS: Seventeen events corresponding to 7.5% of patients and 0.52 per 1000 doses were reported. Seven episodes of rhinitis (two in two patients), three of oral itching, and one of abdominal pain were self-limiting. Two cases of urticaria and two of abdominal pain/nausea were controlled by a temporary dose-adjustment, and one case of urticaria and conjunctivitis required oral antihistamines. Medical intervention was needed in six patients only during a 3-year period. CONCLUSION: The results of this study, performed in a real situation of clinical practice, confirm the satisfactory safety profile of SLIT.     

The nose-lung interaction in allergic rhinitis and asthma: united airways disease

The link between upper and lower respiratory tracts has been repeatedly observed in the past 50 years but only carefully investigated during the past decade. Several clinical and experimental observations suggested the hypothesis of the unity of upper and lower airways (allergic rhinobronchitis or united airways disease). The relationships between rhinitis (and sinusitis) and asthma also include non-epidemiological aspects such as viral infections and bronchial hyperreactivity. The hypotheses have been confirmed by means of epidemiological observations, functional and immunological evidence and, indirectly, by observing the effects of drugs used mainly for rhinitis on asthma symptoms. In this article, therefore, we collected and reviewed the most relevant experimental results available to support the hypothesis for united airways disease and the studies conducted on the possible mechanisms of nose-lung interaction.     

Evaluation of ultrasonic scaling unit waterline contamination after use of chlorine dioxide mouthrinse lavage

BACKGROUND: An infection control problem in dental operatories which is not fully controlled is waterline contamination by heterotrophic mesophilic bacteria. These bacteria are present in water supplies as a planktonic phase and adhere to the lumen of tubings as a biofilm comprised of their external cell surface glycocalyx and by production of extracellular carbohydrate polymers. The adherent film is most difficult to remove. The accumulated planktonic phase can be reduced significantly by flushing water from the lines before use in patient treatment, but will return when the equipment is idle through the accumulation of more planktonic phase and by slough of the biofilm surface-adsorbed phase not yet enmeshed in the carbohydrate matrix. Chlorine dioxide has antimicrobial activity against many bacteria, spores, and viruses. It is used in water supply treatment as a disinfectant and slime preventive and has an advantage over chlorine in that carcinogenic trihalomethanes are not generated. METHODS: This study compared use of phosphate buffer-stabilized chlorine dioxide (0.1%) mouthrinse as a lavage in ultrasonic dental scaler units with the use of tap water as a control. Sterile water flushed through the units onto heterotrophic plate count (HPC) sampler plates was cultured 7 days at room temperature and colonies were counted at 12x. One test and one control unit were used for biopsy of internal tubing and scanning electron microscopy imaging. RESULTS: The HPC counts, in colony forming units (CFU)/ml, were reduced 3- to 5-fold by flushing tap water through the units, but they returned after units were idle overnight. When phosphate-buffered chlorine dioxide mouthrinse was used as a lavage, CFU/ml were reduced 12- to 20-fold. Holding chlorine dioxide in waterlines overnight reduced recurrent buildup compared to water (P <0.05). Scanning electron microscopy images indicated a significant reduction of biofilm coverage by chlorine dioxide as compared to water (P<0.001). CONCLUSIONS: Phosphate-buffered chlorine dioxide mouthrinse was effective in these short-term trials for control of waterline contamination in ultrasonic dental scaling units. It should prove as useful in dental professional waterline applications as it has in industrial uses for biofilm control.     

The natural history of respiratory allergy: a follow-up study of 99 patients up to 10 years

A strict relationship between allergic rhinitis and allergic asthma has been seen recently, and in many ways respiratory allergy could be seen as a single disorder of the airways. The link between rhinitis and asthma can be elucidated only by studying the natural history of the disease over long periods. We describe the follow-up of 99 allergic patients up to 10 years and the evolution of their disease. Ninety-nine patients (50 male, 49 female, mean age 31 years) out of 142, suffering from allergic rhinitis or allergic asthma, could be monitored up to 10 years after the initial diagnosis. Demographics, sensitizations and smoke habit were assumed as evaluation parameters. At baseline, 44 patients suffered from AR alone, 12 from AA alone and 43 from AR+AA. After 10 years, 31.8% of the AR patients developed developed AA and 50% of the patients with AA developed AR. Only the familial history for atopy significantly influenced the disease's evolution, whereas gender, age, smoking habit and skin sensitization did not. Sixty-five percent of patients with a single sensitization at the beginning developed new sensitizations. In conclusion, this long-term survey confirms that a relevant percentage of patients with AR alone or AA alone have a progression of the disease.     

Using the congestion quantifier seven-item test to assess change in patient symptoms and their impact.

Generally, nasal congestion is reported to be the most troublesome symptom of allergic rhinitis and has been shown to have negative effects on sleep, productivity, work, and school performance. A new patient-reported outcome (PRO) tool called the Congestion Quantifier Seven-Item Test (CQ7) was developed and shown to be a reliable and valid screening tool for nasal congestion. The purpose of this study was to assess the CQ7 as a tool for clinical use that can monitor changes in nasal congestion or determine if patients are showing meaningful improvement in symptoms. This study examined the responsiveness of the CQ7 to changes in nasal congestion and changes in relevant PRO to explore whether the CQ7 can serve as a monitoring tool and a valid screening tool for nasal congestion using latent growth curve models. Results showed that the CQ7 is sensitive to changes in patients' symptoms and their impact. Change in the CQ7 from baseline to day 15 was highly related to the change in symptom scores from baseline to day 15 (beta = -0.99); and regression coefficients for the relationships between the CQ7 and changes in the other PRO subscales also were very high (betas ranged from -0.79 to -0.95), lending evidence to support the use of the CQ7 as a monitoring tool. The large sizes of the coefficients suggest that the efficient, seven-item monitoring tool captures change in congestion very well. Analyses of responsiveness to change suggest that a three- to four-point improvement is meaningful to patients.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

Interobserver variation in the interpretation of abdominal radiographs

A total of 140 sets of abdominal radiographs were reviewed independently by four qualified diagnostic radiologists. The degree of interobserver agreement was determined by calculating kappa values for 19 commonly used radiographic signs and diagnoses. There was fair to excellent interobserver agreement for 11 signs and diagnoses and poor agreement for the remaining eight. The signs and diagnoses for which agreement is poor cannot be considered reliable and include particularly large bowel obstruction and nonspecific gas pattern.