Impact of acute exacerbations of COPD on patients' health status beyond pulmonary function: A scoping review.

This scoping review summarized the evidence regarding the impact of acute exacerbations of COPD (AECOPD) on patients' health status beyond pulmonary function. PubMed, Embase, and Web of Science were searched. Prospective cohort studies assessing the health status of patients with COPD in a stable phase of the disease and after a follow-up period (where at least one AECOPD occurred) were included. An integrated assessment framework of health status (i.e., physiological functioning, complaints, functional impairment, quality of life) was used. Twenty-two studies were included. AECOPD acutely affected exercise tolerance, quadriceps muscle strength, physical activity levels, symptoms of dyspnoea and fatigue, and impact of the disease. Long-term effects on quadriceps muscle strength, symptoms of dyspnoea and depression, and quality of life were found. Repeated exacerbations negatively impacted the fat-free mass, levels of dyspnoea, impact of the disease and quality of life. Conflicting evidence was found regarding the impact of repeated exacerbations on exercise tolerance and physical activity levels. AECOPD have well-established acute and long-term adverse effects on health status beyond pulmonary function; nevertheless, the recovery trajectory and the impact of repeated exacerbations are still poorly studied. Further prospective research is recommended to draw firm conclusions on these aspects.

Topographical and functional characterization of the ssDNA probe layer generated through EDC-mediated covalent attachment to nanocrystalline diamond using fluorescence microscopy.

The covalent attachment method for DNA on nanocrystalline diamond (NCD), involving the introduction of COOH functionalities on the surface by photoattachment of 10-undecenoic acid (10-UDA), followed by the 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)-mediated coupling to NH 2-labeled ssDNA, is evaluated in terms of stability, density, and functionality of the resulting biological interface. This is of crucial importance in DNA biosensor development. The covalent nature of DNA attachment will infer the necessary stability and favorable orientation to the ssDNA probe molecules. Using confocal fluorescence microscopy, the influence of buffer type for the removal of excess 10-UDA and ssDNA, the probe ssDNA length, the probe ssDNA concentration, and the presence of the COOH-linker on the density and functionality of the ssDNA probe layer were investigated. It was determined that the most homogeneously dense and functional DNA layer was obtained when 300 pmol of short ssDNA was applied to COOH-modified NCD samples, while H-terminated NCD was resistant for DNA attachment. Exploiting this surface functionality dependence of the DNA attachment efficiency, a shadow mask was applied during the photochemical introduction of the COOH-functionalities, leaving certain regions on the NCD H-terminated. The subsequent DNA attachment resulted in a fluorescence pattern corresponding to the negative of the shadow mask. Finally, NCD surfaces covered with mixtures of the 10-UDA linker molecule and a similar molecule lacking the COOH functionality, functioning as a lateral spacer, were examined for their suitability in preventing nonspecific adsorption to the surface and in decreasing steric hindrance. However, purely COOH-modified NCD samples, patterned with H-terminated regions and treated with a controlled amount of probe DNA, proved the most efficient in fulfilling these tasks.

Towards a real-time, label-free, diamond-based DNA sensor.

Most challenging in the development of DNA sensors is the ability to distinguish between fully complementary target ssDNA (single-strand DNA) and 1-mismatch ssDNA. To deal with this problem, we performed impedance spectroscopy on DNA-functionalized nanocrystalline diamond (NCD) layers during hybridization and denaturation. In both reactions, a difference in behavior was observed for 1-mismatch target DNA and complementary target DNA in real-time. During real-time hybridization, a decrease of the impedance was observed at lower frequencies when the complementary target DNA was added, while the addition of 1-mismatch target ssDNA caused no significant change. Fitting these results to an electrical circuit demonstrates that this is correlated with a decrease of the depletion zone in the space charge region of the diamond. During real-time denaturation, differentiation between 1-mismatch and complementary target DNA was possible at higher frequencies. Denaturation of complementary DNA showed the longest exponential decay time of the impedance, while the decay time during 1-mismatch denaturation was the shortest. The real-time hybridization and denaturation experiments were carried out on different NCD samples in various buffer solutions at temperatures between 20 and 80 degrees C. It was revealed that the best results were obtained using a Microhyb hybridization buffer at 80 degrees C and 10x PCR buffer at 30 degrees C for hybridization and 0.1 M NaOH at temperatures above 40 degrees C for denaturation. We demonstrate that the combination of real-time hybridization spectra and real-time denaturation spectra yield important information on the type of target. This approach may allow a reliable identification of the mismatch sequence, which is the most biologically relevant.

EDC-mediated DNA attachment to nanocrystalline CVD diamond films.

Chemical vapour deposited (CVD) diamond is a very promising material for biosensor fabrication owing both to its chemical inertness and the ability to make it electrical semiconducting that allows for connection with integrated circuits. For biosensor construction, a biochemical method to immobilize nucleic acids to a diamond surface has been developed. Nanocrystalline diamond is grown using microwave plasma-enhanced chemical vapour deposition (MPECVD). After hydrogenation of the surface, 10-undecenoic acid, an omega-unsaturated fatty acid, is tethered by 254 nm photochemical attachment. This is followed by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC)-mediated attachment of amino (NH(2))-modified dsDNA. The functionality of the covalently bound dsDNA molecules is confirmed by fluorescence measurements, PCR and gel electrophoresis during 35 denaturation and rehybridisation steps. The linking method after the fatty acid attachment can easily be applied to other biomolecules like antibodies and enzymes.

What is the optimal treatment strategy for chronic obstructive pulmonary disease exacerbations?

The present study aims to determine whether treating chronic obstructive pulmonary disease (COPD) exacerbations with intravenous steroids and aerosol bronchodilators (group I) is superior to oral steroids and multiple dose inhaler (MDI) bronchodilators with a spacer (group II). Group I received 40 mg methylprednisolone x day(-1) intravenously with a decrease to 20 mg after 10 days and a further decrease of 4 mg x 4 days(-1). Aerosol therapy consisted of 10 mg salbutamol and 1 mg ipratropiumbromide x day(-1). Group II received 32 mg methylprednisolone orally for 1 week followed by 24 mg x day(-1) for 4 days and a subsequent decrease of 4 mg x week(-1). Duovent MDI with a spacer was given at a dose of 1.6 mg fenoterol and 640 microg ipratropiumbromide x day(-1). In group I (n=19) forced expiratory volume in one second (FEV1) rose from 0.82+/-0.46 to 0.91+/-0.47 L and average dyspnoea decreased from 6.0+/-1.9 to 4.1+/-2.6 within 10 days. The Chronic Respiratory Disease Index Questionnaire (CRQ) score increased from 78+/-24 to 90+/-24 points after 4 weeks. In group II (n=18) FEV1 increased from 0.70+/-0.27 to 0.90+/-0.29 L, dyspnoea regressed from 6.2+/-2.4 to 2.7+/-2.6 and CRQ from 67+/-17 to 86+/-20. Both groups showed similar results in dropout rate, length of hospital stay and patient satisfaction. In conclusion, the two treatment strategies appear equally effective in treating chronic obstructive pulmonary disease exacerbations, although oral steroids and metered dose inhaler bronchodilators appear associated with a higher risk of hospital re-admission.

Occupational asthma caused by palladium.

Occupational exposure to complex platinum salts is a well-known cause of occupational asthma. Although there is evidence that platinum refinery workers may also be sensitized to other precious metals, such as palladium or rhodium, no instances of occupational asthma due to an isolated sensitization to palladium have been reported. A case is reported of occupational rhinoconjunctivitis and asthma in a previously healthy worker exposed to the fumes of an electroplating bath containing palladium. There was no exposure to platinum. Sensitization to palladium was documented by skin-prick tests. The skin-prick test was positive with Pd(NH3)4Cl2, but not with (NH4)2PdCl4. Corresponding salts of platinum were all negative. A bronchial provocation test with Pd(NH3)4Cl2 (0.0001% for a total of 315 s, followed by 0.001% for a total of 210 s) led to an early decrease in forced expiratory volume in one second (-35%). A similar exposure (0.001% for a total of 16 min) in an unrelated asthmatic gave no reaction. This case shows that an isolated sensitization to palladium can occur and that respiratory exposure to palladium is a novel cause of metal-induced occupational asthma.