Frost halos from supercooled water droplets

Water freezing on solid surfaces is ubiquitous in nature. Even though icing/frosting impairs the performance and safety in many processes, its mechanism remains inadequately understood. Changing atmospheric conditions, surface properties, the complexity of icing physics, and the unorthodox behavior of water are the primary factors that make icing and frost formation intriguing and difficult to predict. In addition to its unquestioned scientific and practical importance, unraveling the frosting mechanism under different conditions is a prerequisite to develop “icephobic” surfaces, which may avoid ice formation and contamination. In this work we demonstrate that evaporation from a freezing supercooled sessile droplet, which starts explosively due to the sudden latent heat released upon recalescent freezing, generates a condensation halo around the droplet, which crystallizes and drastically affects the surface behavior. The process involves simultaneous multiple phase transitions and may also spread icing by initiating sequential freezing of neighboring droplets in the form of a domino effect and frost propagation. Experiments under controlled humidity conditions using substrates differing up to three orders of magnitude in thermal conductivity establish that a delicate balance between heat diffusion and vapor transport determines the final expanse of the frozen condensate halo, which, in turn, controls frost formation and propagation.     

Experimental evidence for glass polymorphism in vitrified water droplets

The nature of amorphous ices has been debated for more than 35 years. In essence, the question is whether they are related to ice polymorphs or to liquids. The fact that amorphous ices are traditionally prepared from crystalline ice via pressure-induced amorphization has made a clear distinction tricky. In this work, we vitrify liquid droplets through cooling at ≥10⁶ K ⋅ s⁻¹ and pressurize the glassy deposit. We observe a first order–like densification upon pressurization and recover a high-density glass. The two glasses resemble low- and high-density amorphous ice in terms of both structure and thermal properties. Vitrified water shows all features that have been reported for amorphous ices made from crystalline ice. The only difference is that the hyperquenched and pressurized deposit shows slightly different crystallization kinetics to ice I upon heating at ambient pressure. This implies a thermodynamically continuous connection of amorphous ices with liquids, not crystals.     

Inhaled ultrasonically nebulized distilled water decreases exhaled nitric oxide in asthma

Abstract Exhaled nitric oxide (eNO) is increasingly used as a marker of disease activity in asthma. Inhaled hypertonic saline has been shown to induce bronchoconstriction and to decrease eNO in asthmatic subjects, whereas the effects of hypotonic solutions on eNO in these patients have not been studied. To evaluate the effect of ultrasonically nebulized distilled water (UNDW), an indirect hypotonic stimulus, on eNO, 17 asthmatic patients were enrolled and eNO from lower airways was measured by chemiluminescence. UNDW significantly reduced FEV₁ ≥ 20% in 9 subjects (UNDW+), but had no effect in eight patients (UNDW−). Baseline eNO concentration were found to be 51.3 ± 11.1 ppb in UNDW+ and 32.9 ± 7.5 ppb in UNDW− patients, respectively (p = 0.199, NS). UNDW inhalation significantly decreased eNO (from 51.3 ± 11.1 ppb to 31.0 ± 7.1 ppb in UNDW+ (p < 0.020, n = 9) and from 32.9 ± 7.5 ppb to 26.2 ± 7.3 ppb in UNDW− subjects (p < 0.024, n = 8), respectively). eNO percentage reduction in UNDW+ patients was significantly higher compared with UNDW− subjects (−37 ± 4% vs −23 ± 3%, p = 0.021). There was no correlation between FEV₁ changes and eNO percentage decreases in both UNDW+ and UNDW− subjects. In UNDW+ patients, acute bronchodilation induced by salbutamol caused a recovery in both FEV₁ and eNO, though eNO levels remained lower than baseline values. We concluded that UNDW inhalation can significantly decrease eNO in asthmatic patients, either responders or nonresponders to this indirect osmotic challenge; the reduction in eNO levels was only partly dependent on acute changes in airway caliber.     

Inhaled Insulins

The inhalation of insulin was conceptualized by the mid-1920s, but the first successful testing of inhaled insulin occurred in the mid-1990s. The lung has proven to be an organ well capable of absorbing insulin in a reproducible and dose-dependent manner. At present, two concepts of pulmonary insulin delivery at relatively advanced stages of development have been investigated in several published studies. The first involves the Exubera device, a system consisting of a formulation of insulin in a dry and amorphous powder, which is then packaged into blisters. A special delivery system generates a pulse of compressed air, which causes the insulin to form a white fog in a transparent reservoir that can be inhaled by deep breathing. The second approach is the AERx insulin Diabetes Management System, which uses an aqueous formulation of insulin, delivered as an aerosol generated by a special, microprocessor-controlled, inhalation device. This device is capable of monitoring the patient's inspiratory flow and guiding the inhalation by a microelectronic feedback system. The therapeutic efficacy and safety of these inhaled insulins seem comparable to those of subcutaneous insulin regimens; however, inhaled insulins do not appear to achieve significantly better glycemic control. Several other concepts for the pulmonary delivery of insulin are also being developed. With the incidence of diabetes mellitus, especially type 2 diabetes, dramatically increasing worldwide, patients with type 2 diabetes appear to be an important target group for new modalities of insulin delivery. In this group, the onset of insulin treatment is frequently delayed due to the fear of self-injection, preventing effective glycemic control. Patient acceptance of inhaled insulins is excellent and no serious adverse effects have been observed to date. Further advantages of inhaled insulins are the more rapid onset of insulin action and a mitigation of postprandial glucose excursions. However, there are some open questions. The most important concerns the possible long-term effects of insulin inhalation on the lung, as insulin is known to have growth-promoting properties. Thus far, there are no observations of the effects of inhaled insulin on lung structure and function that extend beyond 10 years. In patients with pulmonary disease, the smaller cumulative alveolar surface may cause problems in absorption, and in smokers the action of inhaled insulin has been shown to be stronger and with a faster onset. Furthermore, treatment with inhaled insulin requires larger doses of insulin compared with the subcutaneous route of insulin administration to achieve the same systemic effect, and the costs of this therapy could therefore be significantly higher than the costs of present insulin therapies.     

Inhaled insulin

Inhaled insulin has attractive pharmacodynamic properties with a fast onset of action which should lead to improved postprandial blood glucose concentrations. Comparisons with regular subcutaneous (sc) insulin in clinical studies, however, showed lower fasting blood glucose concentrations. Overall, clinical efficacy of inhaled insulin was comparable to that of regular sc insulin. Treatment with inhaled insulin was safe and well tolerated, with slight and reversible changes in lung function parameters and a rise in insulin antibodies (not associated with any clinical or safety parameters) as main adverse effects. Treatment satisfaction in open-label studies was higher with inhaled than with sc insulin, indicating that inhaled insulin might help to overcome one of the major hurdles of diabetes therapy, i.e. a timely initiation of insulin therapy. The first inhaled insulin formulation was approved in the US and Europe in January 2006, but some countries granted reimbursement only for selected patients, or did not reimburse treatment with inhaled insulin at all because of the high treatment costs. These are due to the rather low bioavailability of approximately 8-15%. Therefore, further research is needed to improve the bioavailability of inhaled insulin: e.g. through optimization of the inhaler, the insulin formulation, or the inhalation technique. In view of the potential for further improvement, inhaled insulin may become a very attractive alternative to sc insulin, in particular in patients in whom insulin therapy has to be initiated and/or intensified.     

Inhaled insulin

Inhalation is a potentially viable route of insulin administration. This treatment is being tested but has not been approved by the United States Food and Drug Administration (FDA). The lung airways contain bronchial tubes, which are impermeable to insulin and alveoli, from which insulin can be absorbed into the circulation. Inhaled asthma medications deposit before reaching the alveoli. Novel devices can deliver insulin particles via slow even breaths into the alveoli. An aerosol of either powdered or solubilized insulin can be released mechanically or electronically. Pulmonary toxicity due to inhaled insulin has not been reported, but no chronic use studies have been conducted. The efficiency of insulin delivery by inhalation may be compromised by: (1) losses within the device and the environment; (2) deposition onto the throat and bronchial tubes; and (3) incomplete absorption from the alveoli. With current delivery technology, the maximum possible delivery efficiency is approximately 30%. The peak activity of inhaled regular insulin occurs at 60 minutes, which is similar to that of subcutaneous lispro insulin. Inhaled long-acting insulin is in early development. Studies comparing sequentially administered subcutaneous and inhaled regular insulins have demonstrated significantly reproducible glucose-lowering effects of inhaled insulin. In type 1 and insulin-treated type 2 patients, substitution of premeal inhaled insulin for subcutaneous insulin has resulted in no significant change in control. In a series of patients with type 2 diabetes failing oral agents, addition of premeal inhaled insulin resulted in significantly improved control. Inhaled insulin will become established if ongoing studies continue to demonstrate this technology to be safe and effective.     

From the Cover: Condensing water vapor to droplets generates hydrogen peroxide

It was previously shown [J. K. Lee et al., Proc. Natl. Acad. Sci. U.S.A., 116, 19294–19298 (2019)] that hydrogen peroxide (H₂O₂) is spontaneously produced in micrometer-sized water droplets (microdroplets), which are generated by atomizing bulk water using nebulization without the application of an external electric field. Here we report that H₂O₂ is spontaneously produced in water microdroplets formed by dropwise condensation of water vapor on low-temperature substrates. Because peroxide formation is induced by a strong electric field formed at the water–air interface of microdroplets, no catalysts or external electrical bias, as well as precursor chemicals, are necessary. Time-course observations of the H₂O₂ production in condensate microdroplets showed that H₂O₂ was generated from microdroplets with sizes typically less than ∼10 µm. The spontaneous production of H₂O₂ was commonly observed on various different substrates, including silicon, plastic, glass, and metal. Studies with substrates with different surface conditions showed that the nucleation and the growth processes of condensate water microdroplets govern H₂O₂ generation. We also found that the H₂O₂ production yield strongly depends on environmental conditions, including relative humidity and substrate temperature. These results show that the production of H₂O₂ occurs in water microdroplets formed by not only atomizing bulk water but also condensing water vapor, suggesting that spontaneous water oxidation to form H₂O₂ from water microdroplets is a general phenomenon. These findings provide innovative opportunities for green chemistry at heterogeneous interfaces, self-cleaning of surfaces, and safe and effective disinfection. They also may have important implications for prebiotic chemistry.

Water molecules in liquid water are considered stable and inert. We and other investigators have reported that water molecules become electrochemically active and catalytic for various reactions when bulk water is formed into micrometer-sized droplets (microdroplets). Reaction rates for various chemical reactions are accelerated in microdroplets by factors of 10² or more compared to bulk solution (1). The microdroplet environment provides conditions for a lowered entropic barrier, which allows thermodynamically unfavorable reactions to proceed in microdroplets at room temperature (2, 3). We also have shown that water microdroplets induce spontaneous charge exchanges between solutes and water molecules to induce the spontaneous reduction of organic molecules and metal ions as well as the formation of nanostructures without any added reducing agent or template (4, 5). Moreover, we have reported that water molecules undergo spontaneous oxidation to form reactive oxygen species, including hydroxyl radicals (OH) and hydrogen peroxide (H₂O₂) (6–8). Recent investigations attributed the origin of these unique physicochemical properties observed in microdroplets to the enrichment of reactants at the interface (9–11), restricted molecular rotations (12), partial solvation at the water surface (1, 13), and a strong interfacial electric field at the surface of the water microdroplet (14).Microdroplets can be formed either by atomizing bulk water (top down) with various methods such as high-pressure gas nebulization (15), ultrasonic nebulization (16), vibrating micromesh nebulization (17), and piezoelectric nebulization (18), or by condensing vapor-phase molecules (bottom up) (19). A question may be asked whether those unique properties of microdroplets arise only in microdroplets formed by atomization of bulk water. In addition, it may be wondered whether the spontaneous oxidation of water to form H₂O₂ in microdroplets (6) was caused by the atomizing process involving friction or vibration. These questions motivated us to investigate whether H₂O₂ becomes spontaneously generated in water microdroplets formed by the condensation of water vapor in air on cold surfaces, and how universal might this process be. We have paid special attention to the influence of different surface properties, including hydrophilicity and surface roughness, as well as environmental factors, including relative humidity and surface temperature.     

Inhaled antimicrobial therapy

Although antimicrobial therapy has been administered through the inhaled route for decades, it has always been controversial. There are relatively few accepted indications for this mode of administration. Well-controlled studies of aerosolized antibiotics in cystic fibrosis demonstrate that tobramycin on a cyclical basis may reduce sputum volume, bacterial counts, and improve pulmonary function. Preliminary data indicate that inhaled antibiotic therapy of ventilator-associated tracheobronchitis may reduce sputum volume, but the clinical significance of this finding remains to be determined. Inhaled pentamidine is used for prophylaxis of Pneumocystis carinii in patients with human immunodeficiency virus infection who are intolerant of oral prophylactic agents. Ribavirin has been used for 30 years to treat respiratory syncytial virus. The role, if any, of inhaled antifungal therapy with amphotericin B remains undetermined.     

Inhaled nitric oxide

Inhaled NO offers a novel therapy for the treatment of pulmonary hypertensive diseases and the symptomatic relief of hypoxemia. The use of iNO reduces the necessity for ECMO in newborns and infants with acute hypoxemic respiratory failure. Proper indications, contraindications, dosing criteria, and implications of the toxic actions of NO must be delineated fully. Randomized clinical trials of patients with carefully defined, specific acute disease states that are characterized by pulmonary hypertension or hypoxemia have not been completed.     

Long-Acting Inhaled Beta Agonists

The development of long-acting inhaled beta agonists has resulted in a new class of asthma medication combining the unparalleled efficacy of beta₂-selective inhaled agents with the long duration of action previously achieved only by systemic bronchodilators. The two agents in this class are salmeterol (Serevent) and formoterol. Salmeterol was introduced in the United States in April 1994 after several years of availability in Europe and has been enthusiastically embraced by both patients and physicians. Still, as with the shorter-acting beta agonists, concerns persist regarding salmeterol's safety. Formoterol still awaits Food and Drug Administration approval in the United States, but shares many of salmeterol's attributes.     

Airborne water droplets in mist or fog may affect nocturnal attacks in asthmatic children.

Our study objectives were to evaluate whether or not airborne water droplets in mist or fog affect the occurrence of nocturnal attacks of asthmatic children using a retrospective study. This study included 971 visits by children with bronchial asthma to the emergency department at nighttime (from 18:00 to 09:00) during a 3-year period (April 1, 1998-March 31, 2001). Meteorological data were checked at a local fire station and regional meteorological observatory. We divided nighttime into five 3-hour periods to evaluate the relationship between chronological changes in the frequency of the emergency department visits of asthmatic children and of meteorological conditions. In four of five periods of nighttime, multivariate analysis showed that mist or fog, average atmospheric temperature, and barometric pressure were related to the number of emergency department visits (n=1096, r=0.165-0.263, p<0.0001). We divided the year into four seasons to eliminate differences between atmospheric temperature and barometric pressure on clear nights and on misty or foggy nights; we also found the mean number of emergency department visits was higher on misty or foggy nights than on clear nights in each seasonal period (p<0.01). In addition, average atmospheric temperature on misty or foggy nights with the emergency department visits was higher than that on misty or foggy nights without any visits (p<0.01). Asthmatic children frequently visited the emergency department on misty or foggy nights, especially during midnight to dawn periods with high atmospheric temperature. Because a higher atmospheric temperature on misty or foggy nights indicates a larger saturated amount of airborne water droplets, our results suggest that mist and fog, in particular a saturated amount of airborne water droplets, may be a stimulus for bronchoconstriction.     

一氧化氮毒副作用的研究

目的：以透射电镜观察吸入一氧化氮（ＮＯ）后肺血管内皮亚细胞结构的改变。　　方法：伴有肺动脉高压的先天性心脏病病人,在接受手术治疗前,全麻状态下,吸入不同时间的ＮＯ。取其肺组织以透射电镜观察肺血管内皮亚细胞结构的改变。　　结果：肺血管内皮有细胞内和间质可复性轻度水肿,与吸入ＮＯ时间不成正比。　　结论：虽然ＮＯ有很多毒副作用,只要有合理的送气系统和严格的监测手段,在短时间的治疗中是无毒副作用的。