Novel inhalation therapy in pulmonary fibrosis: principles, applications and prospects.

Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged.

The future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease in various GOLD groups: a focus on the GOLD 2017 and GOLD 2023 reports.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report revised the combined assessment, merged the C and D groups into the E group, and revised the initial inhalation therapy recommendation. OBJECTIVES: This study aimed to analyze the future exacerbation and mortality of different inhalation therapies among patients with chronic obstructive pulmonary disease (COPD) in various groups based on the GOLD 2017 and GOLD 2023 reports. DESIGN: This is a multicenter and retrospective study. METHODS: Stable COPD patients from the database setup by 12 hospitals were enrolled. The patients were divided into Groups A, B, C, D, and E according to the GOLD 2017 and GOLD 2023 reports. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS subgroups. Data on exacerbation and death during 1 year of follow-up were collected. RESULTS: A total of 4623 patients were classified into Group A (15.0%), Group B (37.8%), Group C (7.3%), Group D (39.9%), and Group E (47.2%). The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies in Groups A and C. Patients treated with LABA + LAMA or LABA + LAMA + ICS had a lower incidence of exacerbation and frequent exacerbation than patients treated with LAMA or LABA + ICS in Groups B, D, and E. The exacerbation, frequent exacerbation, and mortality showed no differences between different inhalation therapies after combining Groups A with C. CONCLUSION: Patients in Group A should be recommended to undergo mono-LAMA, while patients in Groups B and E should be recommended treatment with LABA + LAMA, which is consistent with the GOLD 2023 report. However, it is worth considering merging Groups A and C into a single group and recommending mono-LAMA as the initial inhalation therapy.

The effects of different inhalation therapies on less symptomatic chronic obstructive pulmonary disease patients in a Chinese population: a real-world study.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients. PATIENTS AND METHODS: This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting ß2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data. RESULTS: We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients. CONCLUSION: Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients.KEY MESSAGESOver half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world.The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.

Successful Treatment of an Infant Case of Apnea Caused by Rhinovirus Infection with High-flow Nasal Cannula / 日本プライマリ・ケア連合学会誌

The case involved a one-month-old male infant. Around two weeks after birth, cold-like symptoms were observed within the family. Over the course of approximately one month, the infant gradually developed coughing, apnea, and cyanosis, leading to a visit to a nearby medical facility. The episodes of apnea were initiated by a wet-sounding, choking cough. Respiratory pathogen multiplex screening revealed rhinovirus infection. The infant was managed in the intensive care unit and treated with a high-flow nasal cannula (HFNC), which resulted in an improvement of the recurrent episodes of apnea. We discontinued HFNC on the 7th day of hospitalization; however, the patient had recurrence of apnea. After relieving abdominal distension through rectal enema, the infant was successfully weaned off HFNC and discharged on the 14th day of hospitalization. In addition to the immaturity of the respiratory center in infants, laryngeal chemoreflex triggered by chemical receptors in the larynx is known to contribute to apnea. In the present case, we considered that the reduction of respiratory effort through HFNC, the expectorant effect of warmed and humidified air, and the decrease in gastroesophageal reflux due to alleviation of abdominal distension played roles in the successful outcome.

[Hyperbaric oxygen therapy : Selected indications in the discipline of otorhinolaryngology]. / Hyperbare Sauerstofftherapie : Ausgewählte Indikationen im Fachgebiet HNO-Heilkunde.

Hyperbaric oxygenation (HBO) represents the controlled exposure to positive pressure with simultaneous inhalation of pure oxygen. It is considered to be an effective treatment option for diseases with restricted blood flow as oxygen not only binds chemically to hemoglobin but also physically dissolves in blood plasma. With the help of a hyperbaric chamber the ambient pressure of a patient can be modified and the physiological characteristics in positive pressure can be medically used. The indications relevant to otorhinolaryngology are necrotizing otitis externa and skull base osteomyelitis, other forms of osteomyelitis, gangrene, wound healing disorders and sudden loss of hearing. When choosing a treatment, not only the availability and costs of HBO treatment play a role but also the patient's tolerance of overpressure. The risks of treatment, e.g., due to oxygen toxicity or barotrauma of the middle ear or the paranasal sinuses, must be weighed up against the potential benefits.

Theoretical effectiveness of steam inhalation against SARS-CoV-2 infection: updates on clinical trials, mechanism of actions, and traditional approaches.

Steam inhalation therapy can be a contemporary approach for COVID-19 affected patients of all age groups to manage respiratory conditions, though it presently lacks the scientific backing to establish itself as a befitting practice. The age of COVID-19 has facilitated this traditional home remedy to resurface among the general mass as a helpful approach for the prevention and adjuvant treatment of the disease. In this review, the means of SARS-CoV-2 infection and impact of the parameters, namely steam inhalation and heat on such infection has been delineated via enumerating the effect of the parameters in the human body and against SARS-CoV-2. The literature search was conducted using PubMed, Web of Science, Scopus, ScienceDirect, Wiley Online Library, Google Scholar, and CNKI Scholar databases. The keywords used in the survey include 'Steam inhalation', 'SARS-CoV-2', 'COVID-19', 'Clinical study', 'Mechanism of action', 'Traditional uses', 'Phytochemistry' and 'Adverse effects'. Clinical studies concerning steam inhalation by COVID-19 patients have been comprehended to demarcate the scientific obscurity of the practice. The safety profile of the procedure has also been outlined emphasizing evading measures against COVID-19 and other related disease states. To recapitulate, application of the steam inhalation with herbal concoctions and phytochemicals having folkloric prevalence as an inhalable remedy against respiratory illnesses has been explored in this review work to focus on a new aspect in the COVID-19 treatment paradigm using steam and progress of further research hither.

Real-World Effectiveness of Inhalation Therapy Among Patients With Symptomatic COPD in China: A Multicenter Prospective Study.

Purpose: This real-world study evaluated the effectiveness of different inhalation therapies in patients with symptomatic chronic obstructive pulmonary disease (COPD) in China and also explored the relevant factors that influence the effectiveness of inhalation therapy. Patients and Methods: We conducted a multicenter prospective longitudinal study that was carried out in 12 hospitals in China from December 2016 to June 2021. A face-to-face interview was conducted to collect data. Baseline data were collected at the first visit. Minimum clinically important difference (MCID) was defined as attaining a COPD assessment test (CAT) decrease ≥2. We mainly assessed the MCID and the incidence of exacerbations at the 6 months follow-up. Results: In 695 patients, the mean age was 62.5 ± 8.2 years, with a mean CAT score of 15.1 ± 6.0. Overall, 341 (49.1%) patients attained the MCID of CAT and the incidence of exacerbation during follow-up was 22.3%. Females were significantly more likely to attain MCID than male in COPD patients (adjusted odd ratio (aOR) = 1.93, adjusted 95% confidence interval (a95%CI) = 1.09-3.42, p = 0.024). Patients treated with LABA/LAMA or ICS/LABA/LAMA (ICS, inhaled corticosteroid; LABA, long-acting ß2-agonist; LAMA, long-acting muscarinic antagonist) were more likely to attain MCID than patients treated with LAMA (aOR = 3.97, a95%CI = 2.48-6.35, p < 0.001; aOR = 3.17, a95%CI = 2.09-4.80, p < 0.001, respectively). Patients treated with LABA/LAMA had a higher incidence of severe exacerbation than patients treated with ICS/LABA/LAMA (aOR = 1.95, a95%CI = 1.04-3.66, p = 0.038). Conclusion: The incidence of MCID in symptomatic COPD patients treated with inhalation therapy was nearly 50%. Patients treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID than patients treated with LAMA. Patients treated with LABA/LAMA had a higher incidence of severe exacerbations than with ICS/LABA/LAMA.

Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics.

Over the past years, advanced in vitro pulmonary platforms have witnessed exciting developments that are pushing beyond traditional preclinical cell culture methods. Here, we discuss ongoing efforts in bridging the gap between in vivo and in vitro interfaces and identify some of the bioengineering challenges that lie ahead in delivering new generations of human-relevant in vitro pulmonary platforms. Notably, in vitro strategies using foremost lung-on-chips and biocompatible "soft" membranes have focused on platforms that emphasize phenotypical endpoints recapitulating key physiological and cellular functions. We review some of the most recent in vitro studies underlining seminal therapeutic screens and translational applications and open our discussion to promising avenues of pulmonary therapeutic exploration focusing on liposomes. Undeniably, there still remains a recognized trade-off between the physiological and biological complexity of these in vitro lung models and their ability to deliver assays with throughput capabilities. The upcoming years are thus anticipated to see further developments in broadening the applicability of such in vitro systems and accelerating therapeutic exploration for drug discovery and translational medicine in treating respiratory disorders.

Therapeutic Effect and Mechanisms of Essential Oils in Mood Disorders: Interaction between the Nervous and Respiratory Systems.

Essential oils (EOs) are extracted from plants and contain active components with therapeutic effects. Evidence shows that various types of EOs have a wide range of health benefits. In our previous studies, the potential of lavender EO for prevention and even treatment of depression and anxiety symptoms was demonstrated. The favourable outcomes may be due to multiple mechanisms, including the regulation of monoamine level, the induction of neurotrophic factor expression, the regulation of the endocrine system and the promotion of neurogenesis. The molecules of EOs may reach the brain and exert an effect through two distinctive pathways, namely, the olfactory system and the respiratory system. After inhalation, the molecules of the EOs would either act directly on the olfactory mucosa or pass into the respiratory tract. These two delivery pathways suggest different underlying mechanisms of action. Different sets of responses would be triggered, such as increased neurogenesis, regulation of hormonal levels, activation of different brain regions, and alteration in blood biochemistry, which would ultimately affect both mood and emotion. In this review, we will discuss the clinical effects of EOs on mood regulation and emotional disturbances as well as the cellular and molecular mechanisms of action. Emphasis will be put on the interaction between the respiratory and central nervous system and the involved potential mechanisms. Further evidence is needed to support the use of EOs in the clinical treatment of mood disturbances. Exploration of the underlying mechanisms may provide insight into the future therapeutic use of EO components treatment of psychiatric and physical symptoms.

Promising phytochemicals of traditional Indian herbal steam inhalation therapy to combat COVID-19 - An in silico study.

BACKGROUND: COVID-19, the presently prevailing global public health emergency has culminated in international instability in economy. This unprecedented pandemic outbreak pressingly necessitated the trans-disciplinary approach in developing novel/new anti-COVID-19 drugs especially, small molecule inhibitors targeting the seminal proteins of viral etiological agent, SARS-CoV-2. METHODS: Based on the traditional medicinal knowledge, we made an attempt through molecular docking analysis to explore the phytochemical constituents of three most commonly used Indian herbs in 'steam inhalation therapy' against well recognized viral receptor proteins. RESULTS: A total of 57 phytochemicals were scrutinized virtually against four structural protein targets of SARS-CoV-2 viz. 3CLpro, ACE-2, spike glycoprotein and RdRp. Providentially, two bioactives from each of the three plants i.e. apigenin-o-7-glucuronide and ellagic acid from Eucalyptus globulus; eudesmol and viridiflorene from Vitex negundo and; vasicolinone and anisotine from Justicia adhatoda were identified to be the best hit lead molecules based on interaction energies, conventional hydrogen bonding numbers and other non-covalent interactions. On comparison with the known SARS-CoV-2 protease inhibitor -lopinavir and RdRp inhibitor -remdesivir, apigenin-o-7-glucuronide was found to be a phenomenal inhibitor of both protease and polymerase, as it strongly interacts with their active sites and exhibited remarkably high binding affinity. Furthermore, in silico drug-likeness and ADMET prediction analyses clearly evidenced the usability of the identified bioactives to develop as drug against COVID-19. CONCLUSION: Overall, the data of the present study exemplifies that the phytochemicals from selected traditional herbs having significance in steam inhalation therapy would be promising in combating COVID-19.

Size distribution of microbial aerosols in overground and subterranean treatment chambers at health resorts.

PURPOSE: to perform comparative analyzes of the size distributions of bacteria and fungi in the air of overground therapy chambers in Szczawnica sanatorium and subterranean inhalation chambers in Bochnia Salt Mine health resort taking into account influence of the season and presence of pathogenic species. METHODS: bioaerosol samples were collected using 6-stage Andersen impactor. Bacterial and fungal aerosol concentrations and size distributions were calculated and isolated microorganisms were taxonomically identified based on their morphological, biochemical, and molecular features. Results: in both treatment rooms and atmospheric (outdoor) air, the acceptable microbial pollution levels were periodically exceeded. The size distribution analyzes revealed that in the case of bacteria - emission from the patients and in the case of fungi - transport with atmospheric (outdoor) air were the major processes responsible for microbiological contamination of indoor premises. The majority of microbial particulates were present in the air of studied premises as single bacterial vegetative cells, spores and fungal conidia or (most commonly) formed small microbial or microbial-dust aggregates. This phenomenon may have a significant effect on patients' actual exposure (especially on those treated for respiratory diseases) in terms of the dose of inhaled particles. CONCLUSIONS: the microbiological quality of the air in sanatoriums and health resorts is a key factor for their therapeutic and prophylactic functions. When microbial pollution crossed the acceptable level, the measures that enable reducing undesirable contamination should be introduced, especially if large groups of patients undergo such therapy.

Efficacy analysis of hyperbaric oxygen therapy in the treatment of severe coronavirus disease 2019 patients / 第二军医大学学报

Objective To explore the potential mechanisms underlying the prominent efficiency of hyperbaric oxygen therapy (HBOT) in the treatment of severe coronavirus disease 2019 (COVID-19) patients. Methods Five COVID-19 patients, aged from 24 to 69 years old, received HBOT after routine therapies failed to stop the deterioration and progressive hypoxemia in General Hospital of the Yangtze River Shipping. The procedure of HBOT was as follows: compressed to 2.0 ATA (0.1 MPa gauge pressure, patient 1) or 1.6 ATA (0.06 MPa gauge pressure, patient 2-5) at a constant rate for 15 min, maintained for 90 min (first treatment) or 60 min (subsequent treatment), then decompressed to normal pressure for 20 min, once a day; the patients inhaled oxygen with the mask of Built-in-Breathing System continuously; and HBOT was ended when the daily mean pulse oxygen saturation (SpO2) in wards was above 95% for two days. The symptoms, respiratory rate (RR), SpO2, arterial blood gas analysis, blood routine, coagulation function, high-sensitivity C-reactive protein (hs-CRP) and chest computed tomography (CT) were collected. Paired t test was used to compare each index before and after treatment. Results After the first HBOT, the symptoms and signs of the five patients began to improve. Supine breathlessness disappeared after HBOT for four times, and digestive tract symptoms completely disappeared and only mild chest pain and breathlessness at rest and in motion remained after HBOT for five times. After finishing HBOT, the RR of the patients was significanlty lower than that before HBOT ([20.80±2.28] min-1 vs [27.20±5.40] min-1, P0.05). Before HBOT, the arterial partial pressure of carbon dioxide (PaCO2) of the patients was (31.48±3.40) mmHg (1 mmHg=0.133 kPa), which was lower than the normal range (35-45 mmHg). After finishing HBOT, arterial partial pressure of oxygen ([130.20±18.58] mmHg), arterial oxygen saturation ([98.40±0.55]%), lymphocyte proportion (0.207 8±0.074 2) and lymphocyte count ([1.09±0.24]×109/L) were significantly higher than those before HBOT ([61.60±15.24] mmHg, [73.20±6.43]%, 0.094 6±0.062 1, and [0.61± 0.35]×109/L), while the levels of fibrinogen ([2.97±0.27] g/L) and hs-CRP ([7.76±6.95] mg/L) were significantly lower than those before HBOT ([4.45±0.94] g/L and [30.36±1.27] mg/L) (all P0.05). All the five patients had typical lung CT imaging changes of severe COVID-19 before HBOT, which were improved after HBOT. Conclusion Systemic hypoxia induced by persistent hypoxemia may be the main reason for the deterioration of severe COVID-19. The respiratory dysfunction of COVID-19 is mainly alveolar gas exchange dysfunction. HBOT may be the best way to correct the progressive hypoxemia which can not be controlled by atmospheric oxygen supply in severe COVID-19 patients. HBOT can provide enough oxygen supply for the continuous hypoxia tissues, and is beneficial to the recovery of immune function, circulatory function and stress level, so as to improve the condition of patients.

Alterações cardiorrespiratórias de pacientes submetidos à oxigenoterapia hiperbárica / Alteraciones cardiorrespiratorias de pacientes sometidos a la oxigenoterapia hiperbárica / Cardiorespiratory alterations in patients undergoing hyperbaric oxygen therapy

RESUMO Objetivo Avaliar modificações cardiorrespiratórias em decorrência de sessão única de oxigenoterapia hiperbárica. Método Estudo aleatorizado com pacientes: grupos-controle e oxigenoterapia hiperbárica. As avaliações ocorreram no início, durante e após a exposição ao oxigênio puro acima de uma atmosfera, durante 2 horas. A pressão arterial sistêmica, saturação periférica de oxigênio, frequência de pulso, volume e capacidade pulmonar, pressões inspiratória e expiratória máximas foram avaliadas. A saturação periférica de oxigênio, frequência de pulso e pressão arterial sistêmica foram avaliadas durante a pressurização na primeira hora. Os dados foram avaliados pelo teste de ANOVA, Mann-Whitney e teste t independente (p<0,05). Resultados Foram avaliados 14 pacientes adultos. No grupo sob terapia (sete sujeitos), idade: 49,57±14,59 anos houve redução da frequência de pulso de 16 batimentos por minuto após 35 minutos de terapia (análise intragrupo), e a saturação periférica de oxigênio foi maior neste mesmo período se comparado ao grupo-controle. Conclusão A oxigenoterapia hiperbárica promove alterações cardiorrespiratórias com o aumento da saturação periférica de oxigênio e redução da frequência de pulso, sem alterar os níveis pressóricos arteriais e a força, volumes e capacidades respiratórios.

RESUMEN Objetivo Evaluar modificaciones cardiorrespiratorias consecuentes de sesión única de oxigenoterapia hiperbárica. Método Estudio aleatorizado con pacientes: grupos de control y oxigenoterapia hiperbárica. Las evaluaciones ocurrieron en el inicio, durante y después de la exposición al oxígeno puro por encima de una atmósfera, durante dos horas. La presión arterial sistémica, saturación periférica de oxígeno, frecuencia de pulso, volumen y capacidad pulmonar, presiones inspiratoria y espiratoria máximas fueron evaluadas. La saturación periférica de oxígeno, frecuencia de pulso y presión arterial sistémica fueron evaluadas durante la presurización en la primera hora. Los datos fueron evaluados por el test de ANOVA, Mann Whitney y prueba t independiente (p<0,05). Resultados Fueron evaluados 14 pacientes adultos. En el grupo bajo terapia (siete sujetos), edad: 49,57±14,59 años, hubo reducción de la frecuencia de pulso de 16 latidos por minuto tras 35 minutos de terapia (análisis intragrupo), y la saturación periférica de oxígeno fue mayor en ese mismo período si comparado con el grupo de control. Conclusión La oxigenoterapia hiperbárica proporciona alteraciones cardiorrespiratorias con el aumento de la saturación periférica de oxígeno y la reducción de la frecuencia de pulso, sin alterar los niveles de presión arteriales y la fuerza, volúmenes y capacidades respiratorios.

ABSTRACT Objective To evaluate cardiorespiratory alterations due to a single session of hyperbaric oxygen therapy. Method Randomized study with patients: a control group and hyperbaric oxygen therapy. Evaluations occurred in the beginning, during, and after exposure to pure oxygen above atmosphere for 2 hours. Systemic blood pressure, peripheral oxygen saturation, pulse rate, lung volume and lung capacity, and maximal inspiratory and expiratory pressures were evaluated. Peripheral oxygen saturation, pulse rate, and systemic blood pressure were evaluated during the pressurizing in the first hour. Data were evaluated by means of ANOVA, Mann-Whitney, and independent t-test (p<0.05). Results A total of 14 adult patients were evaluated. In the group under therapy (seven subjects), aged: 49.57±14.59 years, there was a decrease in the pulse rate of 16 beats per minute after 35 minutes of therapy (intragroup analysis), and the peripheral oxygen saturation was higher within the same period compared to the control group. Conclusion The hyperbaric oxygen therapy promotes cardiorespiratory alterations with the increase of the peripheral oxygen saturation and decrease of the pulse rate, without altering blood pressure levels and the strength, volumes, and respiratory capacities.

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry.

Targeted delivery of nanomedicine/nanoparticles (NM/NPs) to the site of disease (e.g., the tumor or lung injury) is of vital importance for improved therapeutic efficacy. Multimodal imaging platforms provide powerful tools for monitoring delivery and tissue distribution of drugs and NM/NPs. This study introduces a preclinical imaging platform combining X-ray (two modes) and fluorescence imaging (three modes) techniques for time-resolved in vivo and spatially resolved ex vivo visualization of mouse lungs during pulmonary NP delivery. Liquid mixtures of iodine (contrast agent for X-ray) and/or (nano)particles (X-ray absorbing and/or fluorescent) are delivered to different regions of the lung via intratracheal instillation, nasal aspiration, and ventilator-assisted aerosol inhalation. It is demonstrated that in vivo propagation-based phase-contrast X-ray imaging elucidates the dynamic process of pulmonary NP delivery, while ex vivo fluorescence imaging (e.g., tissue-cleared light sheet fluorescence microscopy) reveals the quantitative 3D drug/particle distribution throughout the entire lung with cellular resolution. The novel and complementary information from this imaging platform unveils the dynamics and mechanisms of pulmonary NM/NP delivery and deposition for each of the delivery routes, which provides guidance on optimizing pulmonary delivery techniques and novel-designed NM for targeting and efficacy.

Helium-oxygen mixture: clinical applicability in an intensive care unit / Mistura hélio-oxigênio: aplicabilidade clínica em unidade de terapia intensiva

ABSTRACT Objective To evaluate if distress respiratory decreases after using helium-oxygen mixture in pediatric patients diagnosed with bronchospasm. Methods This is a retrospective, non-randomized study that included patients diagnosed with bronchospasm, who received a helium-oxygen mixture at three time points (30, 60, and 120 minutes) according to the organization protocol singular, and were admitted to the intensive care unit, from January 2012 to December 2013. This protocol includes patients with bronchospasm who sustained a modified Wood score of moderate to severe, even after one hour of conventional treatment. Results Twenty children were included in the study. The mean score of severity of the disease at the initial moment was 5.6 (SD:2.0), and at moment 120 minutes, it was 3.4 (SD: 2.0). The severity score showed a significant improvement as of 30 minutes (p<0.001). Conclusion The use of helium-oxygen mixture proved to be effective in diminishing the respiratory distress score for children with airway obstructions; it should be considered a supplementary therapeutic option, together with drug therapy, in specific clinical situations.

RESUMO Objetivo Avaliar se o desconforto diminui após o uso da mistura hélio-oxigênio em pacientes pediátricos com diagnóstico de broncoespasmo. Métodos Estudo retrospectivo, não randomizado, no qual foram incluídos pacientes com diagnóstico de broncoespasmo que utilizaram a mistura hélio-oxigênio em três momentos (30, 60 e 120 minutos), seguindo o protocolo institucional, internados em unidade de terapia intensiva pediátrica de janeiro de 2012 a dezembro 2013. Este protocolo incluía pacientes com diagnóstico de broncoespasmo que mantivessem escore de Wood modificado de moderado a grave, mesmo após 1 hora de tratamento convencional. Resultados Foram incluídas 20 crianças neste estudo. A média do escore de gravidade da doença no momento zero foi de 5,6 (DP:2,0) e, no momento 120 minutos, 3,4 (DP: 2,0). O escore de gravidade apresentou melhora significante a partir dos 30 minutos (p<0,001). Conclusão A utilização da mistura hélio-oxigênio mostrou-se eficaz na redução do escore de desconforto respiratório de crianças com doenças obstrutivas e deve ser considerada recurso terapêutico complementar à terapia medicamentosa em situações clínicas específicas.

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis

ABSTRACT Purpose To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. Materials and methods Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. Conclusions Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option.

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis.

PURPOSE: To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. MATERIALS AND METHODS: Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. RESULTS: All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. CONCLUSIONS: Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option.

Co-milled API-lactose systems for inhalation therapy: impact of magnesium stearate on physico-chemical stability and aerosolization performance.

CONTEXT: Particle micronization for inhalation can impart surface disorder (amorphism) of crystalline structures. This can lead to stability issues upon storage at elevated humidity from recrystallization of the amorphous state, which can subsequently affect the aerosol performance of the dry powder formulation. OBJECTIVE: The aim of this study was to investigate the impact of an additive, magnesium stearate (MGST), on the stability and aerosol performance of co-milled active pharmaceutical ingredient (API) with lactose. METHODS: Blends of API-lactose with/without MGST were prepared and co-milled by the jet-mill apparatus. Samples were stored at 50% relative humidity (RH) and 75% RH for 1, 5, and 15 d. Analysis of changes in particle size, agglomerate structure/strength, moisture sorption, and aerosol performance were analyzed by laser diffraction, scanning electron microscopy (SEM), dynamic vapor sorption (DVS), and in-vitro aerodynamic size assessment by impaction. RESULTS: Co-milled formulation with MGST (5% w/w) led to a reduction in agglomerate size and strength after storage at elevated humidity compared with co-milled formulation without MGST, as observed from SEM and laser diffraction. Hysteresis in the sorption/desorption isotherm was observed in the co-milled sample without MGST, which was likely due to the recrystallization of the amorphous regions of micronized lactose. Deterioration in aerosol performance after storage at elevated humidity was greater for the co-milled samples without MGST, compared with co-milled with MGST. CONCLUSION: MGST has been shown to have a significant impact on co-milled dry powder stability after storage at elevated humidity in terms of physico-chemical properties and aerosol performance.

[Theoretical basis and clinical benefits of dry salt inhalation therapy]. / A szárazsó-belégzéssel történo kezelés elméleti alapjai és gyakorlati haszna.

Dry salt inhalation (halotherapy) reproduces the microclimate of salt caves, with beneficial effect on health. Sodium chloride crystals are disrupted into very small particles (with a diameter less than 3 µm), and this powder is artificially exhaled into the air of a comfortable room (its temperature is between 20-22 °C, and the relative humidity is low). The end-concentration of the salt in the air of the room will be between 10-30 mg/m(3). The sick (or healthy) persons spend 30-60 minutes in this room, usually 10-20 times. Due to the greater osmotic pressure the inhaled salt diminishes the oedema of the bronchial mucosa, decreases its inflammation, dissolves the mucus, and makes expectoration easier and faster (expectoration of air pollution and allergens will be faster, too). It inhibits the growth of bacteria and, in some case, kills them. Phagocyte activity is also increased. It has beneficial effect on the well being of the patients, and a relaxation effect on the central nervous system. It can prevent, or at least decrease the frequency of the respiratory tract inflammations. It produces better lung function parameters, diminishes bronchial hyperreactivity, which is the sign of decreasing inflammation. Its beneficial effect is true not only in inflammation of the lower respiratory tract, but also in acute or chronic upper airways inflammations. According to the international literature it has beneficial effect for some chronic dermatological disease, too, such as psoriasis, pyoderma and atopic dermatitis. This treatment (called as Indisó) is available under medical control in Hungary, too.

Micronucleus test in peripheral blood of rats treated with hyperbaric oxygen after subtotal splenectomy preserving the lower pole

PURPOSE: To assess the mutagenic potential of the oxygen inhalation therapy (HBO), by means of the micronucleus test, performed in peripheral blood of rats that underwent subtotal splenectomy with lower pole preservation (ESTPI), after HBO sessions or simulations. METHODS: Eighteen male Wistar rats, were distributed into three groups of six animals: group 1 - submitted to ESTPI and HBO sessions; group 2 - submitted to ESTPI and HBO simulations; group 3 - underwent cyclophosphamide administration. In groups 1 and 2, blood samples from the animals' tails were collected before surgery (T0) and immediately after the 13th HBO session or simulation (T1). In group 3, tail blood samples were collected from animals before (T0) and 24 hours after (T1) cyclophosphamide (CP) delivery. The number of micronucleated normochromatic erythrocytes (MNNCE) was determined by blind counting 2000 normochromatic erythrocytes (NCE) per animal. RESULTS: Micronuclei average after CP delivery in group 3 was higher than before its use, thus confirming the mutagenic activity of this drug (p=0.01). In groups 1 and 2, no significant difference in the average of Micronuclei was observed when comparing it to blood samples before and after the 13th HBO session or simulation. CONCLUSION: The treatment protocol used in this study did not induce Micronucleus formation in animals submitted to ESTPI and HBO treatment or simulation. .