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1.
Nat Commun ; 15(1): 8468, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349461

RESUMO

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio <0.70 and an FEV1 ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.


Assuntos
Acetilcisteína , Pulmão , Doença Pulmonar Obstrutiva Crônica , Humanos , Acetilcisteína/administração & dosagem , Acetilcisteína/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Método Duplo-Cego , Volume Expiratório Forçado/efeitos dos fármacos , Adulto , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Idoso de 80 Anos ou mais , Resultado do Tratamento , Progressão da Doença , Capacidade Vital/efeitos dos fármacos , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Testes de Função Respiratória , Expectorantes/administração & dosagem , Expectorantes/uso terapêutico
2.
BMC Pulm Med ; 24(1): 434, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223526

RESUMO

BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.


Assuntos
Acetilcisteína , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Acetilcisteína/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Feminino , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Volume Expiratório Forçado/efeitos dos fármacos , Administração por Inalação , Capacidade Vital/efeitos dos fármacos , Expectorantes/administração & dosagem , Expectorantes/efeitos adversos , Resultado do Tratamento
5.
Pharm Biol ; 59(1): 321-334, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33770452

RESUMO

CONTEXT: Kyeongok-go (KOG) is a traditional mixed herb preparation consisting of Panax ginseng CA Meyer (Araliaceae), Poria cocos Wolf (Polyporaceae), Rehmannia glutinosa (Gaertner) Liboschitz ex Steudel (Orobanchaceae), and honey. Various pharmacological effects of KOG are reported, but the efficacy on respiratory diseases has not been evaluated. OBJECTIVE: The anti-inflammatory, expectorant, and antitussive properties of KOG were examined using animal models of respiratory diseases. MATERIALS AND METHODS: KOG (100, 200, and 400 mg/kg) was orally administered to ICR mice (n = 8) once a day for 11 days. Anti-inflammatory effects of vehicle, xylene, KOG and DEXA (1 mg/kg) were determined by monitoring edoema and redness of treated ears, and measuring the relative and absolute weight of each ear. Expectorant properties of vehicle, KOG and AM (250 mg/kg) were evaluated by observing body surface redness, and the amount of mucous secreted by the trachea. The antitussive potential of vehicle, NH4OH, KOG and TB (50 mg/kg) was evaluated by monitoring changes in the number of coughs (for 6 min). RESULTS: KOG (400 mg/kg) treated mice showed 31.29% and 30.72% (p < 0.01) decreases in the relative and absolute weights of each ear relative to xylene control mice, 39.06% increases (p < 0.01) in TLF OD values relative to intact vehicle control mice, and 59.53% decrease (p < 0.01) in coughing compared to NH4OH control mice. Dose-dependent changes were observed in all experimental models. CONCLUSIONS: KOG may be a potential therapeutic agent for the treatment of various respiratory diseases, particularly those caused by environmental toxins.


Assuntos
Anti-Inflamatórios/farmacologia , Antitussígenos/farmacologia , Expectorantes/farmacologia , Extratos Vegetais/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Antitussígenos/administração & dosagem , Tosse/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expectorantes/administração & dosagem , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem
6.
Respir Med ; 175: 106190, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33217537

RESUMO

BACKGROUND: International guidelines recommend mucolytic agents as add-on therapy in selected patients with COPD because they may reduce exacerbations and improve health status. As the evidence varies among mucolytic agents, we used the Delphi method to assess consensus amongst an international panel of COPD experts on mucolytics use in COPD. METHODS: 53 COPD experts from 12 countries were asked to complete an online questionnaire and rate their agreement with 15 statements using a 5-point scale. The mucolytic agents evaluated were carbocysteine, erdosteine and N-acetylcysteine (NAC). Data were collected anonymously and consensus presented using descriptive statistics. RESULTS: The 47 respondents reached consensus on the statements. They agreed that regular treatment with mucolytic agents effectively reduces the frequency of exacerbations, reduces the duration of mild-to-moderate exacerbations, and can increase the time to first exacerbation and symptom-free time in COPD patients. Consensus was consistently highest for erdosteine. The experts agreed that all three mucolytics display antioxidant and anti-inflammatory activity. Erdosteine and NAC were thought to improve the efficacy of some classes of antibacterial drugs. All three mucolytics were considered effective for the short-term treatment of symptoms of acute exacerbations when added to other drugs. The panel agreed that approved doses of mucolytic agents have favorable side-effect profiles and can be recommended for regular use in patients with a bronchitic phenotype. CONCLUSIONS: Consensus findings support the wider use of mucolytic agents as add-on therapy for COPD. However, the differences in pharmacological actions and clinical effectiveness must be considered when deciding which mucolytic to use.


Assuntos
Acetilcisteína/uso terapêutico , Carbocisteína/uso terapêutico , Consenso , Expectorantes/uso terapêutico , Guias de Prática Clínica como Assunto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Exacerbação dos Sintomas , Tioglicolatos/uso terapêutico , Tiofenos/uso terapêutico , Acetilcisteína/administração & dosagem , Acetilcisteína/efeitos adversos , Carbocisteína/administração & dosagem , Carbocisteína/efeitos adversos , Quimioterapia Combinada , Expectorantes/administração & dosagem , Expectorantes/efeitos adversos , Feminino , Nível de Saúde , Humanos , Internacionalidade , Masculino , Inquéritos e Questionários , Tioglicolatos/administração & dosagem , Tioglicolatos/efeitos adversos , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Resultado do Tratamento
7.
Eur J Pharm Biopharm ; 157: 200-210, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33222771

RESUMO

Nowadays, the resistance of bacterial biofilms towards the available antibiotics is a severe problem. Therefore, many efforts were devoted to develop new formulations using nanotechnology. We have developed an inhalable microparticle formulation using spray-drying combining multiple drugs: an antibiotic (tobramycin, ciprofloxacin or azithromycin), N-acetylcysteine (NAC), and curcumin (Cur). The use of PLGA nanoparticles (NP) also allowed incorporating curcumin to facilitate spray drying and modify the release of some compounds. The aerosolizable microparticles formulations were characterized in terms of size, morphology, and aerodynamic properties. Biocompatibility when tested on macrophage-like cells was acceptable after 20 h exposure for concentrations up to at least 32 µg/mL. Antibacterial activity of free drugs versus drugs in the multiple drug formulations was evaluated on P. aeruginosa in the same range. When co-delivered the efficacy of tobramycin was enhanced compared to the free drug for the 1 µg/mL concentration. The combinations of azithromycin and ciprofloxacin with NAC and Cur did not show an improved antibacterial activity. Bacteria-triggered cytokine release was not inhibited by free antibiotics, except for TNF-α. In contrast, the application of NAC and the addition of curcumin-loaded PLGA NPs showed a higher potential to inhibit TNF-α, IL-8, and IL-1ß release. Overall, the approach described here allows simultaneous delivery of antibacterial, mucolytic, and anti-inflammatory compounds in a single inhalable formulation and may therefore pave the way for a more efficient therapy of pulmonary infections.


Assuntos
Acetilcisteína/administração & dosagem , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Curcumina/administração & dosagem , Portadores de Fármacos , Expectorantes/administração & dosagem , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Infecções por Pseudomonas/tratamento farmacológico , Acetilcisteína/química , Acetilcisteína/metabolismo , Administração por Inalação , Antibacterianos/química , Antibacterianos/metabolismo , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Azitromicina/administração & dosagem , Azitromicina/química , Ciprofloxacina/administração & dosagem , Ciprofloxacina/química , Curcumina/química , Curcumina/metabolismo , Citocinas/metabolismo , Combinação de Medicamentos , Composição de Medicamentos , Expectorantes/química , Expectorantes/metabolismo , Liofilização , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/microbiologia , Viabilidade Microbiana/efeitos dos fármacos , Muco/metabolismo , Permeabilidade , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Células THP-1 , Tobramicina/administração & dosagem , Tobramicina/química
8.
Pan Afr Med J ; 36: 56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733627

RESUMO

We report a case of a 43-year-old female who presented with a history of recurrent productive cough, since her teenage years. Her associated symptoms included dyspnoea, occasional pleuritic chest pain and rarely, constitutional symptoms. Treated numerous times for lower respiratory tract infections, her symptoms would improve after antimicrobial therapy, but always recurred. She had a background of HIV infection and was virologically suppressed on antiretroviral therapy for nine years. Investigations revealed an active pseudomonas infection and high-resolution computed tomography scan (HRCT) and bronchoscopy confirmed features of Mounier-Kuhn syndrome. The patient was treated accordingly with positive airway pressure, mucolytic agents and chest physiotherapy aimed at aiding mucus clearance and received pneumococcal and influenza vaccines. Mounier-Kuhn syndrome, though rare, should be considered in the differential diagnosis of patients with recurrent lower respiratory tract infections. In Africa, more cases may be identified and treated appropriately with timely investigation and treatment.


Assuntos
Dor no Peito/etiologia , Tosse/etiologia , Dispneia/etiologia , Traqueobroncomegalia/diagnóstico , Adulto , Broncoscopia , Expectorantes/administração & dosagem , Feminino , Humanos , Namíbia , Tomografia Computadorizada por Raios X , Traqueobroncomegalia/terapia
9.
Int J Pharm ; 582: 119304, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32272167

RESUMO

In this paper the innovative approach of nano into micro dry powders (NiM) was applied to incorporate into mannitol or mannitol/cysteamine micromatrices ivacaftor-loaded nanoparticles for pulmonary delivery in CF. Nanoparticles composed by a mixture of two polyhydrohydroxyethtylaspartamide copolymers containing loaded with ivacaftor at 15.5% w/w were produced. The nanoparticles were incorporated into microparticles to obtain NiM that were fully characterized in terms of size, morphology, interactions with artificial Cf mucus (CF-AM) as well as for aerodynamic behaviour. Finally the activity of ivacaftor-containing NiM was evaluated by in vitro preliminary experiments. NiM at matrix composed by a mixture of mannitol:cysteamine showed greater ability to reduce CF-AM viscosity whereas that based on just mannitol showed better aerodynamic properties with a FPF of about 25%. All produced NiM showed very good cytocompatibility and the released ivacaftor was able to restore the chroride transport in vitro.


Assuntos
Aminofenóis/administração & dosagem , Agonistas dos Canais de Cloreto/administração & dosagem , Cisteamina/administração & dosagem , Regulador de Condutância Transmembrana em Fibrose Cística/agonistas , Fibrose Cística/tratamento farmacológico , Expectorantes/administração & dosagem , Manitol/administração & dosagem , Nanopartículas , Peptídeos/química , Quinolonas/administração & dosagem , Administração por Inalação , Aminofenóis/química , Animais , Células Cultivadas , Agonistas dos Canais de Cloreto/química , Cisteamina/química , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Composição de Medicamentos , Liberação Controlada de Fármacos , Expectorantes/química , Manitol/química , Mutação , Pós , Quinolonas/química , Ratos Endogâmicos F344
10.
Trials ; 20(1): 747, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856887

RESUMO

BACKGROUND: Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care. METHODS: This is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum. DISCUSSION: This trial's pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE. TRIAL REGISTRATION: EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017). ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018. Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01). SPONSOR: Belfast Health and Social Care Trust. Ethics Reference Number: 17/NE/0339. Protocol version: v3.0 Final_14052018.


Assuntos
Bronquiectasia/tratamento farmacológico , Carbocisteína/administração & dosagem , Análise Custo-Benefício , Expectorantes/administração & dosagem , Solução Salina Hipertônica/administração & dosagem , Administração por Inalação , Adulto , Carbocisteína/agonistas , Esquema de Medicação , Quimioterapia Combinada/economia , Quimioterapia Combinada/métodos , Expectorantes/economia , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Nebulizadores e Vaporizadores , Ensaios Clínicos Controlados Aleatórios como Assunto , Solução Salina Hipertônica/economia , Escarro/efeitos dos fármacos , Resultado do Tratamento
11.
J Control Release ; 314: 62-71, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31654686

RESUMO

Cystic fibrosis (CF) is a serious lung disease, commonly susceptible to Pseudomonas aeruginosa colonization. The dense mucus together with biofilm formation limit drug permeability and prevent the drug from reaching the site of action, causing treatment failure of the bacterial infection. Besides the use of antibiotics, the mucolytic agent N-acetylcysteine (NAC) is recommended to be co-administered in the treatment of CF. Although several formulations have been developed for inhalation therapy to improve the pulmonary condition in CF patients, there is still no comprehensive study on a combined multifunctional dry powder formulation of antibiotics with NAC. In this work, we developed an innovative multifunctional dry powder inhaler (DPI) formulation based on salt formation between NAC and antibiotics and characterized their solid state properties and physical stability. NAC could be spray dried together with three different antibiotics, azithromycin (Azi), tobramycin (Tobra) and ciprofloxacin (Cipro), without the use of organic solvents to form Azi/NAC, Tobra/NAC and Cipro/NAC DPI formulations. Solid-state characterization of these DPI formulations showed that they were amorphous after spray drying. Azi/NAC and Tobra/NAC form co-amorphous salt systems that were physically stable under storage at stress conditions. For particle characterization, the obtained mass median aerodynamic diameters were in a suitable range for inhalation (< 5.0µm). The multifunctional antibiotic/NAC formulations conserved or improved the antibiotic susceptibility and showed promising results regarding the inhibition of P. aeruginosa PA14 biofilm formation.


Assuntos
Acetilcisteína/administração & dosagem , Antibacterianos/administração & dosagem , Biofilmes/efeitos dos fármacos , Fibrose Cística/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Acetilcisteína/farmacologia , Administração por Inalação , Animais , Antibacterianos/farmacologia , Azitromicina/administração & dosagem , Azitromicina/farmacologia , Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacologia , Fibrose Cística/complicações , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Expectorantes/administração & dosagem , Expectorantes/farmacologia , Cavalos , Muco/microbiologia , Tamanho da Partícula , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , Tobramicina/administração & dosagem , Tobramicina/farmacologia
12.
Pak J Pharm Sci ; 32(3 Special): 1409-1413, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31551222

RESUMO

To observe and analyze the therapeutic efficacy of high-dose ambroxol in the treatment of severe pneumonia, as well as summarize the nursing methods. A total of 180 patients diagnosed with severe pneumonia and treated at our hospital who were enrolled. The patients were divided into a control group and are search group, with 90 patients in each group. Of those, patients in the research group were treated with high-doses ambroxol, while small-dose ambroxol was administered to patients in the control group. The therapeutic efficacy was compared between both groups. Meanwhile, predictive nursing regimens were applied on patients in the research group, while routine nursing care was given to patients in the control group. The nursing satisfaction was compared between both groups. By comparing the pulmonary function indicators, Comparison of procalcitonin (PCT) and C-reactive protein (CRP) results showed that all indicators of the research group were obviously better than those of the control group (p<0.05). The time of infection control, ICU stay and hospital stay of the research group were significantly less than those of the control group (p<0.05). Moreover, the overall nursing satisfaction of the research group was significantly higher than that of the control group (p<0.05).Application of high-dose ambroxol and scientific nursing methods could significantly improve the therapeutic efficacy in the treatment of severe pneumonia and gain favorable nursing satisfaction.


Assuntos
Ambroxol/administração & dosagem , Expectorantes/administração & dosagem , Cuidados de Enfermagem , Pneumonia/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Ambroxol/uso terapêutico , Proteína C-Reativa/análise , Relação Dose-Resposta a Droga , Expectorantes/uso terapêutico , Feminino , Humanos , Unidades de Terapia Intensiva , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Pró-Calcitonina/sangue , Resultado do Tratamento , Adulto Jovem
13.
Eur Rev Med Pharmacol Sci ; 23(15): 6727-6735, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31378916

RESUMO

OBJECTIVE: COPD is one of the major causes of morbidity and mortality worldwide and represents one of the most important issues for public health. Frequent exacerbations induce a faster decline in lung function and poorer quality of life, increase mortality, and have a socio-economic impact with a high burden in terms of resources and healthcare costs. The clinical trials evaluated the effect of mucolytics in COPD and showed that the long-term carbocysteine, associated with bronchodilators, anticholinergics, and steroids, reduces the frequency of exacerbations and improves the quality of life. PATIENTS AND METHODS: The aim of this prospective real-life study was to evaluate the long-term impact on exacerbations (at 1 year) in COPD patients treated with carbocysteine lysine salt (single dose of 2.7 g once a day) in addition to background therapy with or without inhaled steroids. RESULTS: In a total of 155 evaluable patients, our study showed that the addition of a single dose of carbocysteine lysine salt to background therapy determines a statistically significant reduction of the average number of exacerbations vs. the number observed in the previous year (from 1.97±0.10 to 1.03±0.11; p<0.01), irrespective of treatment with or without inhaled steroids. In particular, in patients with ≥2 exacerbations in the previous year, the addition of carbocysteine lysine salt resulted in a statistically significant reduction in the exacerbations rate from 69% to 33% and from 58% to 25%, respectively (p<0.01) in patients with or without inhaled steroids. CONCLUSIONS: In summary, our data highlighted the efficacy of long-term administration of a single daily dose of carbocysteine lysine salt (2.7 g/day) in reducing the number and rate of exacerbations in COPD patients, independently from the use of inhaled steroids.


Assuntos
Broncodilatadores/administração & dosagem , Carbocisteína/análogos & derivados , Expectorantes/administração & dosagem , Glucocorticoides/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbocisteína/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Exacerbação dos Sintomas , Resultado do Tratamento
14.
Respir Med ; 147: 37-43, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30704697

RESUMO

BACKGROUND: N-acetylcysteine (NAC) 600 mg twice daily is a well-tolerated oral antioxidant mucolytic that reduces the risk of moderate to severe chronic obstructive pulmonary disease (COPD) exacerbations. PANTHEON was one of the largest studies to evaluate NAC in COPD. It recruited current, ex- and never-smokers, concomitantly treated with other medications, and used a symptom-based definition of COPD exacerbations rather than the conventional healthcare resource utilisation (HCU) criteria. METHODS: This manuscript reports post-hoc analyses of the PANTHEON dataset investigating whether smoking status or use of concomitant medications influenced the efficacy of NAC in terms of reducing exacerbations, defined according to HCU. RESULTS: Compared with placebo (N = 482), NAC (N = 482) reduced the rate of HCU events by 20% (p = 0.0027), with a larger effect in current/ex-smokers (23%; p < 0.01). In patients receiving NAC and long-acting inhaled bronchodilator(s) but no ICS, there was a 60% reduction in the rate of exacerbations compared to those receiving placebo, long-acting bronchodilator(s) and ICS (p < 0.0001). CONCLUSIONS: Overall, these post-hoc hypothesis-generating analyses confirm that NAC reduces the rate of COPD exacerbations, particularly in patients with COPD who have a significant smoking history, and in those not treated with ICS. NAC may provide an alternative to ICS-containing combinations in these patient subgroups. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR-TRC-09000460.


Assuntos
Acetilcisteína/uso terapêutico , Expectorantes/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fumar/efeitos adversos , Acetilcisteína/administração & dosagem , Administração por Inalação , Administração Oral , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Broncodilatadores/uso terapêutico , China/epidemiologia , Progressão da Doença , Expectorantes/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença
15.
J Gastroenterol Hepatol ; 34(8): 1337-1343, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30734357

RESUMO

BACKGROUND AND AIM: Several strategies have been proposed to increase the eradication rate of Helicobacter pylori. However, the widespread increasing resistance rates to current multiple-dose oral antibiotic therapies call for alternative therapeutic approaches. We aim to develop a novel intraluminal therapy for H. pylori infection (ILTHPI). METHODS: From April 2017 to December 2017, 100 H. pylori-infected treatment-naïve patients with upper abdominal pain or discomfort underwent endoscopic examinations and concomitant ILTHPI, which comprised the control of intragastric pH, the irrigation of gastric mucosal surface with a mucolytic agent, and the application of single-dose medicaments containing antibiotic powders. The safety profiles while conducting ILTHPI and adverse events after ILTHPI were evaluated. The success of eradication was assessed based on the result of the 13 C-urea breath test 6 weeks after ILTHPI. In addition, a patient with successful ILTHPI was reconfirmed by a negative H. pylori stool antigen test four to 6 months after ILTHPI to exclude short-term recurrence. RESULTS: All the 100 enrolled patients completed the ILTHPI with good safety profiles and mild adverse events (6%). Five patients dropped out, and 51 of 95 patients (53.7%) achieved successful eradication immediately after endoscopic examinations. All 51 patients revealed negative stool H. pylori antigen tests four to 6 months after successful ILTHPI. No short-term recurrence was observed. CONCLUSIONS: We have developed a novel therapeutic approach. With the ILTHPI, H. pylori can be eradicated immediately by administrating a single-dose regimen while conducting an endoscopic examination. CLINICAL TRIALS NUMBER: NCT03124420.


Assuntos
Acetilcisteína/administração & dosagem , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Claritromicina/administração & dosagem , Expectorantes/administração & dosagem , Mucosa Gástrica/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Lansoprazol/administração & dosagem , Metronidazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Irrigação Terapêutica , Acetilcisteína/efeitos adversos , Adulto , Idoso , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Claritromicina/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Expectorantes/efeitos adversos , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Concentração de Íons de Hidrogênio , Lansoprazol/efeitos adversos , Masculino , Metronidazol/efeitos adversos , Pessoa de Meia-Idade , Pós , Estudos Prospectivos , Indução de Remissão , Irrigação Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
J Zoo Wildl Med ; 50(3): 570-578, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33517625

RESUMO

Published anesthetic protocols for captive and free-ranging bears are limited to injectable inductions with maintenance via inhalants or additional injectable boluses. Though common in other species, intravenous (IV) continuous-rate infusions (CRI) using guaifenesin combinations have not been evaluated in ursids. This study evaluated the use of a CRI compared to an inhalant for maintenance anesthesia. Seven healthy American black bears (Ursus americanus) were anesthetized in a crossover design with two different anesthetic maintenance protocols. Bears were immobilized with ketamine (2.02 ± 0.14 mg/kg) and medetomidine (0.04 ± 0.003 mg/kg) for both protocols. The anesthetic maintenance control protocol consisted of isoflurane gas (ISO) started at 2% delivered by endotracheal tube; the experimental protocol consisted of guaifenesin, medetomidine, ketamine (GMK) IV CRI started at 50 mg/kg/hr guaifenesin, 0.01 mg/kg/hr medetomidine, and 1 mg/kg/hr ketamine. Induction and recovery parameters including time to first effect, recumbency, and hands on; duration of maintenance protocol; and time from reversals administered to head up, standing on all four feet, no ataxia, and to fully recovered were recorded and compared between protocols. Heart rate, respiratory rate, rectal temperature, blood pressure, end tidal carbon dioxide, and hemoglobin oxygen saturation were recorded at 5-min intervals and compared between protocols. Venous blood gases were obtained at the start, middle, and end of the maintenance anesthesia and compared between protocols. All bears exhibited hypertension with mild respiratory acidosis throughout procedures. Measured physiologic parameters did not differ significantly between the isoflurane and the GMK CRI maintenance protocols, with the exception of higher endpoint (ISO) pCO2 measurements. No adverse events were recorded with either protocol, and adequate depth of anesthesia was maintained with both protocols. GMK CRI provides a safe, effective, and more portable alternative to inhalant anesthetics for maintenance anesthesia in bears in captivity or in the field.


Assuntos
Anestesia Geral/veterinária , Guaifenesina/farmacologia , Isoflurano/farmacologia , Ketamina/farmacologia , Medetomidina/farmacologia , Ursidae , Anestésicos Dissociativos/administração & dosagem , Anestésicos Dissociativos/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Combinação de Medicamentos , Expectorantes/administração & dosagem , Expectorantes/farmacologia , Feminino , Guaifenesina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Injeções Intravenosas , Masculino
17.
Heart Lung ; 48(2): 141-147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30409442

RESUMO

BACKGROUND AND OBJECTIVES: Inhaled mucoactive agents are used to enhance airway clearance, however efficacy and safety are unclear in adults with acute respiratory conditions. METHODS: We systematically reviewed randomized controlled trials assessing respiratory function; safety; length of stay (LOS); mucus; radiology; and oxygenation. RESULTS: No adverse events were reported for dornase alfa (n = 63), N-acetylcysteine (NAC, n = 50), ambroxol (n = 140), hypertonic saline (n = 33), heparin (n = 384), mannitol (n = 20) or isotonic saline. During invasive ventilation, NAC, dornase alfa and saline had no effect on mucus. Postoperatively, mucus characteristics improved with NAC (n = 10). Ambroxol lowered LOS (mean difference 4 days) and halved complications following lung carcinoma resection (n = 140). Heparin improved ventilator-free days (n = 130, mean difference 3.9-4.6) and intensive care LOS (n = 223, 3.2 days), but not ventilator-acquired pneumonia. CONCLUSION: Dornase alfa, hypertonic saline and NAC were ineffective for atelectasis/mucus plugging while intubated. More data are required to support using NAC, ambroxol and heparin during acute illness.


Assuntos
Expectorantes/administração & dosagem , Pneumopatias/tratamento farmacológico , Depuração Mucociliar/efeitos dos fármacos , Doença Aguda , Administração por Inalação , Adulto , Ambroxol/administração & dosagem , Desoxirribonuclease I/administração & dosagem , Humanos , Pneumopatias/metabolismo , Manitol/administração & dosagem , Proteínas Recombinantes/administração & dosagem
18.
Thorac Cancer ; 10(2): 243-248, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30585684

RESUMO

BACKGROUND: Radiation pneumonitis is one of the most harmful and clinically significant complications of radiotherapy. This study investigated the benefits of nebulized acetylcysteine for lung cancer patients diagnosed with radiation pneumonitis after radiotherapy. METHODS: We prospectively enrolled and followed 25 patients with radiation pneumonitis who used nebulized acetylcysteine three times a day for 12 weeks. We also reviewed the medical records of 106 control patients who had undergone radiotherapy for lung cancer but had not used acetylcysteine. We evaluated the effects of nebulized acetylcysteine by comparing visits 1 and 4 among nebulizer users and by comparing the acetylcysteine group with the control group. RESULTS: Twenty-five acetylcysteine group patients and 101 control group patients were included in the analyses. The mean patient-rated severity score associated with sputum production decreased in the acetylcysteine group between visits 1 and 4 (from 1.10 to 0.95; P = 0.08). None of the patients used additional expectorant agents after using nebulized acetylcysteine and critical adverse events were not reported. The acetylcysteine group had a shorter mean duration of expectorant use among patients whose radiation pneumonitis required steroid therapy and covered > 10% of a single lung field on computed tomography (37.2 vs. 78.1 days, respectively; P = 0.07). CONCLUSIONS: The beneficial effects of nebulized acetylcysteine for patients with radiation pneumonitis included relieving sputum severity and minimizing expectorant use, especially in severe cases. Further investigation is required to clarify and expand on the benefits of nebulized acetylcysteine for patients with radiation pneumonitis.


Assuntos
Acetilcisteína/administração & dosagem , Expectorantes/administração & dosagem , Pneumonite por Radiação/tratamento farmacológico , Radioterapia/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
19.
Consult Pharm ; 33(11): 658-666, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30458908

RESUMO

OBJECTIVE: The purpose of this report is to describe the case of a 43-year-old male with asthma who was hospitalized for an exacerbation of non-cystic fibrosis bronchiectasis (NCFB), a chronic lung disease that is characterized by dilation of the airways, persistent cough, chronic sputum production, and recurrent respiratory infections. He was treated with oral and inhaled antibiotics, inhaled bronchodilators, and aggressive airway-clearance techniques including nebulized 7% sodium chloride, flutter valve, and high-frequency chest wall oscillation. SETTINGS: Community pharmacy, nursing facility pharmacy, consultant pharmacy practice. PRACTICE CONSIDERATIONS: As the number of patients diagnosed with NCFB continues to increase, it is crucial to recognize that specific guidance for management of NCFB is warranted, as treatment responses differ from cystic fibrosis bronchiectasis or chronic obstructive pulmonary disease. CONCLUSION: It is important for pharmacists to understand the pharmacologic and nonpharmacologic treatments for NCFB to better assist physicians and patients and improve therapeutic outcomes.


Assuntos
Bronquiectasia/tratamento farmacológico , Administração por Inalação , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Asma/complicações , Bronquiectasia/complicações , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Quimioterapia Combinada , Expectorantes/administração & dosagem , Expectorantes/uso terapêutico , Humanos , Masculino
20.
Pulm Pharmacol Ther ; 53: 80-85, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30352285

RESUMO

Mucoactive drugs are commonly used in the treatment of acute respiratory tract diseases, such as lower and acute respiratory infection and chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) in which an increased mucus secretion is one of main clinical features. Indeed these drugs are designed to promote secretion clearance and to specifically alter the viscoelastic properties of mucus, restoring an effective mucociliary clearance and reducing broncho-obstructive symptoms. In association with mucolytics, these patients frequently also receive antibiotics to reduce the bacterial load, thus decreasing the release of infectious and pro-inflammatory products. Erdosteine is one of the most used mucoactive agents for the treatment of several respiratory diseases where the overlap of bacterial infection is frequent. Although the effectiveness in the reducing mucus in acute and chronic respiratory disease has been demonstrated for others mucolytic, some of them when given in combination with an antibiotic therapy, could reduce the antibiotic efficacy in some situation. Differently, erdosteine potentiates the antibiotic effect when given in combination with antibiotics. We have reviewed the literature available on both clinical and in vitro studies that have investigated this effect of erdosteine on the effect of antibiotics when used as combined therapy.


Assuntos
Expectorantes/administração & dosagem , Doenças Respiratórias/tratamento farmacológico , Tioglicolatos/administração & dosagem , Tiofenos/administração & dosagem , Antibacterianos/administração & dosagem , Quimioterapia Combinada , Humanos , Depuração Mucociliar/efeitos dos fármacos , Muco/metabolismo , Polimedicação , Doenças Respiratórias/fisiopatologia
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