Effects of omalizumab in severe asthmatics across ages: A real life Italian experience.

BACKGROUND: This retrospective study aimed at evaluating long-term effects of Omalizumab in elderly asthmatics in a real-life setting. METHODS: 105 consecutive severe asthmatics (GINA step 4-5; mean FEV1% predicted:66 ± 15.7) treated with Omalizumab for at least 1 year (treatment mean duration 35.1 ± 21.7 months) were divided into 3 groups according to their age at Omalizumab treatment onset: 18-39, 40-64 and ≥ 65 years. RESULTS: Comorbidities, number of overweight/obese subjects and patients with late-onset asthma were more frequent among older people. A similar reduction of inhaled corticosteroids dosage and SABA on-demand therapy was observed in all groups during Omalizumab treatment; a similar FEV1 increased was also observed. Asthma Control Test (ACT) improved significantly (p < 0.001) in the three groups, increasing from 15 [IQR:12-18] to 24 [IQR:22-25] in younger subjects, from 14 [IQR:10-16] to 21 [IQR:20-23] in the 40-64-year-group and from 15 [IQR:12-16] to 20 [IQR:18-22] in elderly patients where improvement was lower (p = 0.039) compared to younger people. Asthma exacerbations decreased significantly after Omalizumab but the percentage of exacerbation-free patients was higher in younger people (76.9%) compared to middle aged patients (49.2%) and the elderly (29%) (p = 0.049). After Omalizumab treatment, the risk for exacerbations was lower in subjects aged 40-64 (OR = 0.284 [CI95% = 0.098-0.826], p = 0.021) and 18-39 (OR = 0.133 [CI95% = 0.026-0.678], p = 0.015), compared to elderly asthmatics. Also, a significantly reduced ACT improvement (ß = -1.070; p = 0.046) passing from each age class was observed. CONCLUSION: Omalizumab improves all asthma outcomes independently of age, although the magnitude of the effects observed in the elderly seems to be lower than in the other age groups.

Can we modulate asthma maintenance treatment level with disease seasonal variations?

Asthma can have clinical seasonal fluctuations due to different exposure factors. The analysis of our data and literature confirm a seasonal trend of asthma severity. In this brief review, authors discuss the possibility to adapt maintenance therapy level to clinical seasonal fluctuations, by increasing treatment in some seasons to prevent exacerbations and by decreasing it in others, when symptoms are low, in order to minimize costs and maximize safety. Literature and our data (concerning studies carried out in areas with a temperate climate) indicate that asthma severity is reduced in summer while it tends to increase in the other seasons. Authors conclude that a preventive increasing maintenance treatment level during the season when we know that patients worsen (starting some weeks before symptom worsening) may reduce asthma exacerbation risks. On the contrary, a summer treatment reduction, in patients that improve during this period, may be considered only in asthma phenotypes with a benign disease course in time.

Influenza A H1N1 and severe asthma exacerbation.

The pandemic influenza A H1N1 will affect millions of subjects. This influenza can cause respiratory complications with possible death. We have described two case reports of acute severe asthma exacerbation combined to influenza A H1N1, caracterized by severe respiratory failure. The diagnosis of influenza A H1N1 was confirmed with the multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay. These patients, apart from asthma, do not have other diseases; but they did not take adequate therapy. In addition to conventional therapy (corticosteroids, bronchodilator and antibiotics) oseltamivir 75 mg bid was immediately added. After few days the patients improved and therefore in a short time they were discharged. During this period, in the case of severe asthma exacerbations, one must always think of influenza A H1N1 as the possible cause. It is necessary to use oseltamivir precociously to avoid severe complications. All asthmatic patients must regularly take their therapy especially during pandemic influenza A H1N1.

Bilirubin photoconversion induced by monochromatic laser radiation. Comparison between aerobic and anaerobic experiments in vitro.

Structural and geometric photoisomerization of bilirubin bound to human serum albumin was investigated. Solutions were irradiated with monochromatic light emitted by an Ar ion laser, the 457.9, 488.0 and 514.5 nm wavelengths being selected. Photoproducts were separated and analysed by h.p.l.c. Visible-absorption spectra of pure ZZ-bilirubin, ZE-bilirubin and lumirubin in the eluent were registered in the 350-550 nm region by collecting single fractions by h.p.l.c. Wavelength-dependence of bilirubin photoconversion was studied within photoequilibrium and up to a large decrement of the total concentration. Experiments were performed in aerobic and anaerobic conditions in order to assess the contribution of the photo-oxidation to the overall process. The presence of O2 was found to increase the rate of bilirubin degradation and unexpectedly to favour lumirubin production. The ability of 514.5 nm irradiation to induce bilirubin cyclization was definitively confirmed.

Laser investigation of bilirubin-photobilirubin photoconversion.

The reversibility of the configurational photoisomerization process of bilirubin (BR) with laser lines in the blue-green spectral region is investigated. Photoisomerization efficiency of BR is found to depend strongly on wavelength, and to decrease when the excitation wavelength is increased from blue to green. Reversion of BR photoisomers (identical to photobilirubin, PBR) back to native BR is demonstrated for several laser lines by irradiating PBR/BR mixtures with wavelengths greater than the excitation wavelengths. Green lines turn out to be very efficient for PBR----BR reversion. The PBR concentrations at photoequilibrium, obtained from the spectrophotometric data, are in close agreement with the corresponding values measured with the high performance liquid chromatography technique in the case of 10 nm bandwidth filtered light reported in the literature. The 457 nm blue laser line produces 32% PBR concentration at photoequilibrium; only 14, 7, and 3% PBR concentrations are produced by the blue-green lines at 488, 501, 514 nm, respectively. The effect on the photostationary PBR/BR mixture of successive irradiations with different wavelengths, and the influence of the wavelength sequence are reported. In the case of blue lines our results support the assumption of the first-order kinetics for the BR in equilibrium PBR photoreaction. Departures are observed with green-lines (501, 514 nm). The present results, together with the i) good clinical efficiency reported for fluorescent green lamps; and ii) slow elimination of configurational photoisomers in infants, tend to confirm the lumirubin-pathway as the main mechanism for phototherapy, and call for clinical investigation of narrow-spectrum lamps with peak emission wavelength in the (biologically safer) 480 divided by 530 nm range.

Green light in phototherapy.

Photodegradation of bilirubin in vivo has been investigated by using green fluorescent sources according to the suggestions obtained in a previous study in vitro. Two groups of 50 jaundiced low-birth-weight infants were exposed to fluorescent light in phototherapy units under similar irradiant conditions. One group was exposed for 24 h to standard green tubes, the other, to daylight lamps. Newborns of the two groups were similar for gestational age, birthweight, and initial bilirubin concentration. A greater decrease in the serum concentration of bilirubin was found in subjects exposed to the green light when compared with infants exposed to daylight lamps. The use of green light is strongly suggested instead of the white, blue, and special blue lamps, because of the real efficiency, power and range of wave lengths.

Laser photolysis of bilirubin.

Photodegradation of bilirubin in vitro has been investigated by using monochromatic light supplied by an argon ion laser selecting the 457.9, 488.0 and 514.5 nm wavelengths. Bilirubin was examined in chloroform, in aqueous solutions and in human serum under different experimental conditions of concentration, laser power and time of irradiance. Photodecomposition was followed by optical density measurements on the absorption maximum of the electronic band at 460 nm. The rate of degradation of bilirubin was found to be only slightly affected by the wavelength of the exciting lines provided they fall within the absorption band. In particular it was shown that any wavelength, lambda, is equally effective if the corresponding absorbance, A lambda, exceeds a minimum value of 5-10%. In the aqueous solutions, light with lambda greater than 470 nm has been found to be largely effective in the photodegradation of bilirubin in vitro.