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Phillippa Poole - One of the best experts on this subject based on the ideXlab platform.

  • The Cochrane Library - Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease
    The Cochrane database of systematic reviews, 2015
    Co-Authors: Phillippa Poole, Jimmy Chong, Christopher J Cates
    Abstract:

    Background Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Personal and healthcare costs associated with exacerbations indicate that any therapy that reduces the occurrence of exacerbations is useful. A marked difference among countries in terms of prescribing of Mucolytics reflects variation in perceptions of their effectiveness. Objectives Primary objective • To determine whether treatment with Mucolytics reduces frequency of exacerbations and/or days of disability in patients with chronic bronchitis or chronic obstructive pulmonary disease. Secondary objectives • To assess whether Mucolytics lead to improvement in lung function or quality of life. • To determine frequency of adverse effects associated with use of Mucolytics. Search methods We searched the Cochrane Airways Group Specialised Register and reference lists of articles on 10 separate occasions, most recently in July 2014. Selection criteria We included randomised studies that compared oral Mucolytic therapy versus placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. Data collection and analysis This review analysed summary data only, most derived from published studies. For earlier versions, one review author extracted data, which were rechecked in subsequent updates. In later versions, review authors double-checked extracted data and then entered data into RevMan for analysis. Main results We added four studies for the 2014 update. The review now includes 34 trials, recruiting a total of 9367 participants. Many studies did not clearly describe allocation concealment; hence selection bias may have inflated the results, which reduces our confidence in the findings. Results of 26 studies with 6233 participants show that the likelihood that a patient could be exacerbation-free during the study period was greater among Mucolytic groups (Peto odds ratio (OR) 1.75, 95% confidence interval (CI) 1.57 to 1.94). However, more recent studies show less benefit of treatment than was reported in earlier studies in this review. The overall number needed to treat with Mucolytics for an additional beneficial outcome for an average of 10 months - to keep an additional participant free from exacerbations - was eight (NNTB 8, 95% CI 7 to 10). Use of Mucolytics was associated with a reduction of 0.03 exacerbations per participant per month (mean difference (MD) -0.03, 95% CI -0.04 to -0.03; participants = 7164; studies = 28; I2 = 85%) compared with placebo, that is, about 0.36 per year, or one exacerbation every three years. Very high heterogeneity was noted for this outcome, so results need to be interpreted with caution. The type or dose of Mucolytic did not seem to alter the effect size, nor did the severity of COPD, including exacerbation history. Longer studies showed smaller effects of Mucolytics than were reported in shorter studies. Mucolytic use was associated with a reduction of 0.43 days of disability per participant per month compared with placebo (95% CI -0.56 to -0.30; studies = 13; I2 = 61%). With Mucolytics, the number of people with one or more hospitalisations was reduced, but study results were not consistent (Peto OR 0.68, 95% CI 0.52 to 0.89; participants = 1788; studies = 4; I2 = 58%). Investigators reported improved quality of life with Mucolytics (MD -2.64, 95% CI -5.21 to -0.08; participants = 2231; studies = 5; I2 = 51%). Although this mean difference did not reach the minimal clinically important difference of -4 units, we cannot assess the population impact, as we do not have the data needed to carry out a responder analysis. Mucolytic treatment was not associated with any significant increase in the total number of adverse effects, including mortality (Peto OR 1.03, 95% CI 0.52 to 2.03; participants = 2931; studies = 8; I2 = 0%), but the confidence interval is too wide to confirm that the treatment has no effect on mortality. Authors' conclusions In participants with chronic bronchitis or COPD, we are moderately confident that treatment with Mucolytics may produce a small reduction in acute exacerbations and a small effect on overall quality of life. Our confidence in the results is reduced by the fact that effects on exacerbations shown in early trials were larger than those reported by more recent studies, possibly because the earlier smaller trials were at greater risk of selection or publication bias, thus benefits of treatment may not be as great as was suggested by previous evidence.

  • Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease
    Cochrane Database of Systematic Reviews, 2015
    Co-Authors: Phillippa Poole, Jimmy Chong, Christopher J Cates
    Abstract:

    Background Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Personal and healthcare costs associated with exacerbations indicate that any therapy that reduces the occurrence of exacerbations is useful. A marked difference among countries in terms of prescribing of Mucolytics reflects variation in perceptions of their effectiveness. Objectives Primary objective • To determine whether treatment with Mucolytics reduces frequency of exacerbations and/or days of disability in patients with chronic bronchitis or chronic obstructive pulmonary disease. Secondary objectives • To assess whether Mucolytics lead to improvement in lung function or quality of life. • To determine frequency of adverse effects associated with use of Mucolytics. Search methods We searched the Cochrane Airways Group Specialised Register and reference lists of articles on 10 separate occasions, most recently in July 2014. Selection criteria We included randomised studies that compared oral Mucolytic therapy versus placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. Data collection and analysis This review analysed summary data only, most derived from published studies. For earlier versions, one review author extracted data, which were rechecked in subsequent updates. In later versions, review authors double-checked extracted data and then entered data into RevMan for analysis. Main results We added four studies for the 2014 update. The review now includes 34 trials, recruiting a total of 9367 participants. Many studies did not clearly describe allocation concealment; hence selection bias may have inflated the results, which reduces our confidence in the findings. Results of 26 studies with 6233 participants show that the likelihood that a patient could be exacerbation-free during the study period was greater among Mucolytic groups (Peto odds ratio (OR) 1.75, 95% confidence interval (CI) 1.57 to 1.94). However, more recent studies show less benefit of treatment than was reported in earlier studies in this review. The overall number needed to treat with Mucolytics for an additional beneficial outcome for an average of 10 months - to keep an additional participant free from exacerbations - was eight (NNTB 8, 95% CI 7 to 10). Use of Mucolytics was associated with a reduction of 0.03 exacerbations per participant per month (mean difference (MD) -0.03, 95% CI -0.04 to -0.03; participants = 7164; studies = 28; I2 = 85%) compared with placebo, that is, about 0.36 per year, or one exacerbation every three years. Very high heterogeneity was noted for this outcome, so results need to be interpreted with caution. The type or dose of Mucolytic did not seem to alter the effect size, nor did the severity of COPD, including exacerbation history. Longer studies showed smaller effects of Mucolytics than were reported in shorter studies. Mucolytic use was associated with a reduction of 0.43 days of disability per participant per month compared with placebo (95% CI -0.56 to -0.30; studies = 13; I2 = 61%). With Mucolytics, the number of people with one or more hospitalisations was reduced, but study results were not consistent (Peto OR 0.68, 95% CI 0.52 to 0.89; participants = 1788; studies = 4; I2 = 58%). Investigators reported improved quality of life with Mucolytics (MD -2.64, 95% CI -5.21 to -0.08; participants = 2231; studies = 5; I2 = 51%). Although this mean difference did not reach the minimal clinically important difference of -4 units, we cannot assess the population impact, as we do not have the data needed to carry out a responder analysis. Mucolytic treatment was not associated with any significant increase in the total number of adverse effects, including mortality (Peto OR 1.03, 95% CI 0.52 to 2.03; participants = 2931; studies = 8; I2 = 0%), but the confidence interval is too wide to confirm that the treatment has no effect on mortality. Authors' conclusions In participants with chronic bronchitis or COPD, we are moderately confident that treatment with Mucolytics may produce a small reduction in acute exacerbations and a small effect on overall quality of life. Our confidence in the results is reduced by the fact that effects on exacerbations shown in early trials were larger than those reported by more recent studies, possibly because the earlier smaller trials were at greater risk of selection or publication bias, thus benefits of treatment may not be as great as was suggested by previous evidence.

  • Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
    The Cochrane database of systematic reviews, 2012
    Co-Authors: Phillippa Poole, Peter N. Black, Christopher J Cates
    Abstract:

    Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of Mucolytics depending on whether or not they are perceived to be effective. to determine if treatment with Mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both. to determine if Mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with Mucolytics. We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012. We included randomised studies that compared oral Mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis. Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the Mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with Mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of Mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with Mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants. In participants with chronic bronchitis or COPD, treatment with a Mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.

  • Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease
    Cochrane Database of Systematic Reviews, 2012
    Co-Authors: Phillippa Poole, Peter N. Black
    Abstract:

    Background: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of Mucolytics depending on whether or not they are perceived to be effective. Primary objective: to determine if treatment with Mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both. Secondary objectives: to determine if Mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with Mucolytics. Search methods: We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012. Selection criteria: We included randomised studies that compared oral Mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. Data collection and analysis: The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis. Main results: Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the Mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with Mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of Mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with Mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants. Authors' conclusions: In participants with chronic bronchitis or COPD, treatment with a Mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.

  • The Cochrane Library - Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
    The Cochrane database of systematic reviews, 2010
    Co-Authors: Phillippa Poole, Peter N. Black
    Abstract:

    Background: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of Mucolytics depending on whether or not they are perceived to be effective. Primary objective: to determine if treatment with Mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both. Secondary objectives: to determine if Mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with Mucolytics. Search methods: We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012. Selection criteria: We included randomised studies that compared oral Mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. Data collection and analysis: The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis. Main results: Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the Mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with Mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of Mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with Mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants. Authors' conclusions: In participants with chronic bronchitis or COPD, treatment with a Mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.

Peter N. Black - One of the best experts on this subject based on the ideXlab platform.

  • Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
    The Cochrane database of systematic reviews, 2012
    Co-Authors: Phillippa Poole, Peter N. Black, Christopher J Cates
    Abstract:

    Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of Mucolytics depending on whether or not they are perceived to be effective. to determine if treatment with Mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both. to determine if Mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with Mucolytics. We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012. We included randomised studies that compared oral Mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis. Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the Mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with Mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of Mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with Mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants. In participants with chronic bronchitis or COPD, treatment with a Mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.

  • Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease
    Cochrane Database of Systematic Reviews, 2012
    Co-Authors: Phillippa Poole, Peter N. Black
    Abstract:

    Background: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of Mucolytics depending on whether or not they are perceived to be effective. Primary objective: to determine if treatment with Mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both. Secondary objectives: to determine if Mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with Mucolytics. Search methods: We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012. Selection criteria: We included randomised studies that compared oral Mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. Data collection and analysis: The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis. Main results: Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the Mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with Mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of Mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with Mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants. Authors' conclusions: In participants with chronic bronchitis or COPD, treatment with a Mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.

  • The Cochrane Library - Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
    The Cochrane database of systematic reviews, 2010
    Co-Authors: Phillippa Poole, Peter N. Black
    Abstract:

    Background: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of Mucolytics depending on whether or not they are perceived to be effective. Primary objective: to determine if treatment with Mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both. Secondary objectives: to determine if Mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with Mucolytics. Search methods: We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012. Selection criteria: We included randomised studies that compared oral Mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. Data collection and analysis: The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis. Main results: Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the Mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with Mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of Mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with Mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants. Authors' conclusions: In participants with chronic bronchitis or COPD, treatment with a Mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.

  • Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
    The Cochrane database of systematic reviews, 2006
    Co-Authors: P J Poole, Peter N. Black
    Abstract:

    Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of Mucolytics depending on whether or not they are perceived to be effective. To assess the effects of oral Mucolytics in adults with stable chronic bronchitis or COPD. We have searched the Cochrane Airways Group Specialised Register and reference lists of articles on four separate occasions, the most recent being in June 2005. This is the third major update. Randomised trials that compared oral Mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded. One reviewer extracted data. Study authors and drug companies were contacted for missing information. Twenty six trials were included (7335 participants). Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral Mucolytics (weighted mean difference (WMD) -0.05 per month, 95% confidence interval -0.05, -0.04). Using the annualised rate of exacerbations in the control patients of 2.6 per year, this is a 20% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35). A recent study has shown that the benefit may apply only to those patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the Mucolytic group (OR 2.13 (95% CI 1.86 to 2.42)). There was no difference in lung function or in adverse effects reported between the treatments. In subjects with chronic bronchitis or COPD, treatment with Mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. They should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.

  • Preventing Exacerbations of Chronic Bronchitis and COPD
    American Journal of Respiratory Medicine, 2003
    Co-Authors: Phillippa J. Poole, Peter N. Black
    Abstract:

    It is important to find interventions that will reduce the frequency and severity of exacerbations of COPD, because of their effect on morbidity and healthcare expenditure. A Cochrane systematic review included 23 studies that had evaluated the effects of treatment with Mucolytic agents in patients with chronic bronchitis or COPD. Mucolytic treatment was associated with a significant reduction of 0.79 exacerbations per patient per year compared with placebo, a 29% decrease. Patients who received treatment with Mucolytic agents were twice as likely to remain exacerbation-free in the study period than if they had received placebo, with six patients needing regular treatment with Mucolytic agents for 3–6 months to achieve one less exacerbation over that time. Treatment with Mucolytic agents resulted in nearly 7 days less illness per patient per year. How Mucolytic agents work is unknown, although they may reduce exacerbations by altering mucus production, antioxidation, or antibacterial or immunostimulatory effects. They do not appear to affect the decline in lung function that occurs in COPD. The treatment appears to be without any adverse effects, apart from the need to take oral medication daily. Cost-effectiveness analysis suggests that the point at which the costs of treatment and non-treatment were equal was 1.2 less exacerbations per year. This is higher than the effect observed in the Cochrane review, suggesting that treating everyone with COPD with Mucolytic agents would not be cost effective. Those with more frequent and severe exacerbations appear to have the most to gain.

David L. Morris - One of the best experts on this subject based on the ideXlab platform.

  • assessment of a novel Mucolytic solution for dissolving mucus in pseudomyxoma peritonei an ex vivo and in vitro study
    Pleura and peritoneum, 2017
    Co-Authors: Krishna Pillai, Javed Akhter, David L. Morris
    Abstract:

    Background Pseudomyxoma peritonei (PMP) is difficult to treat. Intraperitoneal delivery of Mucolytic solutions might potentially improve therapy, in addition to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy. Methods Comparison of Mucolytic effect of two formulations (control: bromelain 300 µg/mL+N-Acetylcystein 250 mM; test: bromelain 200 µg/mL+200 mM cysteamine) in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 PMP patients. Mucin plugs were classified according to their density into three categories: hard, semi hard and soft. Simulation of peritoneal washing ex vivo using a closed heated circulating pump. Results Solubilisation was faster with the test vs. the control formulation (90 vs. 180 min) for dissolving the soft mucin plugs (p < 0.05). The test solution was also more effective in dissolving the hard mucus plugs compared to control (82.5±2.74 % vs. 36.33±3.27 %). All mucin types disintegrated in simulated peritoneal washing. Cytotoxicity of the test solution on HT29 cell line was time-dependent. Conclusions The test formulation is more effective and faster than the control formulation in dissolving mucus plugs of various densities. Mucus plugs were all solubilised after 40 min in simulated peritoneal washing. This novel Mucolytic formulation might pave the way for an effective and less invasive therapy of PMP in the future.

  • Assessment of a novel Mucolytic solution for dissolving mucus in pseudomyxoma peritonei: an ex vivo and in vitro study.
    Pleura and peritoneum, 2017
    Co-Authors: Krishna Pillai, Javed Akhter, David L. Morris
    Abstract:

    Background Pseudomyxoma peritonei (PMP) is difficult to treat. Intraperitoneal delivery of Mucolytic solutions might potentially improve therapy, in addition to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy. Methods Comparison of Mucolytic effect of two formulations (control: bromelain 300 µg/mL+N-Acetylcystein 250 mM; test: bromelain 200 µg/mL+200 mM cysteamine) in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 PMP patients. Mucin plugs were classified according to their density into three categories: hard, semi hard and soft. Simulation of peritoneal washing ex vivo using a closed heated circulating pump. Results Solubilisation was faster with the test vs. the control formulation (90 vs. 180 min) for dissolving the soft mucin plugs (p 

  • Efficacy of a novel Mucolytic agent on pseudomyxoma peritonei mucin, with potential for treatment through peritoneal catheters.
    American journal of cancer research, 2014
    Co-Authors: Javed Akhter, Krishna Pillai, Terence C. Chua, Naeef Alzarin, David L. Morris
    Abstract:

    Compared to current treatment for pseudomyxoma peritonei (PMP), the extraction of solubilised mucin through peritoneal catheter can be minimally invasive. However, mucin has variable appearance that may influence mucolysis. Hence, we investigated the mucolysis of 36 mucin samples with a novel agent. Using visual inspection and hardness index, PMP mucin was classified into three grades. The mucin pathological category was identified from patient record. Subsequently, the dissolution of the samples was tested. For in vitro, 1 g of mucin was treated to the Mucolytic agent in 10 ml TRIS buffer at 37 deg. Celsius for 3 hours, with weighing of residual mucin. Control treatment was similar but received TRIS buffer. For in vivo, 2 g of implanted intra-peritoneal mucin in nude rats was treated to Mucolytic (2 X 500 ul/24 hr, over 48 hours, plus another treatment before sacrifice at 56 hours, with weighing of residual mucin. Controls were treated but only with TRIS buffer. Six animals were used for each mucin grade (3 Mucolytic treated & and 3 controls). Grades of mucin were soft mucin (62%), semi hard (20%) and hard mucin (18%). Diffuse peritoneal adenomucinosis had 50% of soft mucin and peritoneal mucinous carcinoma had 11% (P = 0.0382). In vitro and in vivo absolute disintegration was 100% for soft, 57.38% and 48.67% for semi hard, 50% and 28.67% for hard mucin. Majority of mucin were soft with complete disintegration, the rest showed variable disintegration, suggesting that the Mucolytic has potential for treating PMP.

  • Potential Mucolytic agents for mucinous ascites from pseudomyxoma peritonei.
    Investigational new drugs, 2012
    Co-Authors: Krishna Pillai, Javed Akhter, Terence C. Chua, David L. Morris
    Abstract:

    Pseudomyxoma peritonei is a disease characterised by the accumulation of mucinous ascites. Thus far, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be effective at eradicating disease. Chemotherapy has been less effective, providing disease stabilization but not demonstrating significant treatment responses. Mucolytic is a potential class of drug that may be exploited in the chemical management of this disease. A variety of potential Mucolytic agents are explored in this review providing evidence of basic biochemical evidence of its efficacy with potential translational application.

Christopher J Cates - One of the best experts on this subject based on the ideXlab platform.

  • The Cochrane Library - Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease
    The Cochrane database of systematic reviews, 2015
    Co-Authors: Phillippa Poole, Jimmy Chong, Christopher J Cates
    Abstract:

    Background Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Personal and healthcare costs associated with exacerbations indicate that any therapy that reduces the occurrence of exacerbations is useful. A marked difference among countries in terms of prescribing of Mucolytics reflects variation in perceptions of their effectiveness. Objectives Primary objective • To determine whether treatment with Mucolytics reduces frequency of exacerbations and/or days of disability in patients with chronic bronchitis or chronic obstructive pulmonary disease. Secondary objectives • To assess whether Mucolytics lead to improvement in lung function or quality of life. • To determine frequency of adverse effects associated with use of Mucolytics. Search methods We searched the Cochrane Airways Group Specialised Register and reference lists of articles on 10 separate occasions, most recently in July 2014. Selection criteria We included randomised studies that compared oral Mucolytic therapy versus placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. Data collection and analysis This review analysed summary data only, most derived from published studies. For earlier versions, one review author extracted data, which were rechecked in subsequent updates. In later versions, review authors double-checked extracted data and then entered data into RevMan for analysis. Main results We added four studies for the 2014 update. The review now includes 34 trials, recruiting a total of 9367 participants. Many studies did not clearly describe allocation concealment; hence selection bias may have inflated the results, which reduces our confidence in the findings. Results of 26 studies with 6233 participants show that the likelihood that a patient could be exacerbation-free during the study period was greater among Mucolytic groups (Peto odds ratio (OR) 1.75, 95% confidence interval (CI) 1.57 to 1.94). However, more recent studies show less benefit of treatment than was reported in earlier studies in this review. The overall number needed to treat with Mucolytics for an additional beneficial outcome for an average of 10 months - to keep an additional participant free from exacerbations - was eight (NNTB 8, 95% CI 7 to 10). Use of Mucolytics was associated with a reduction of 0.03 exacerbations per participant per month (mean difference (MD) -0.03, 95% CI -0.04 to -0.03; participants = 7164; studies = 28; I2 = 85%) compared with placebo, that is, about 0.36 per year, or one exacerbation every three years. Very high heterogeneity was noted for this outcome, so results need to be interpreted with caution. The type or dose of Mucolytic did not seem to alter the effect size, nor did the severity of COPD, including exacerbation history. Longer studies showed smaller effects of Mucolytics than were reported in shorter studies. Mucolytic use was associated with a reduction of 0.43 days of disability per participant per month compared with placebo (95% CI -0.56 to -0.30; studies = 13; I2 = 61%). With Mucolytics, the number of people with one or more hospitalisations was reduced, but study results were not consistent (Peto OR 0.68, 95% CI 0.52 to 0.89; participants = 1788; studies = 4; I2 = 58%). Investigators reported improved quality of life with Mucolytics (MD -2.64, 95% CI -5.21 to -0.08; participants = 2231; studies = 5; I2 = 51%). Although this mean difference did not reach the minimal clinically important difference of -4 units, we cannot assess the population impact, as we do not have the data needed to carry out a responder analysis. Mucolytic treatment was not associated with any significant increase in the total number of adverse effects, including mortality (Peto OR 1.03, 95% CI 0.52 to 2.03; participants = 2931; studies = 8; I2 = 0%), but the confidence interval is too wide to confirm that the treatment has no effect on mortality. Authors' conclusions In participants with chronic bronchitis or COPD, we are moderately confident that treatment with Mucolytics may produce a small reduction in acute exacerbations and a small effect on overall quality of life. Our confidence in the results is reduced by the fact that effects on exacerbations shown in early trials were larger than those reported by more recent studies, possibly because the earlier smaller trials were at greater risk of selection or publication bias, thus benefits of treatment may not be as great as was suggested by previous evidence.

  • Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease
    Cochrane Database of Systematic Reviews, 2015
    Co-Authors: Phillippa Poole, Jimmy Chong, Christopher J Cates
    Abstract:

    Background Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Personal and healthcare costs associated with exacerbations indicate that any therapy that reduces the occurrence of exacerbations is useful. A marked difference among countries in terms of prescribing of Mucolytics reflects variation in perceptions of their effectiveness. Objectives Primary objective • To determine whether treatment with Mucolytics reduces frequency of exacerbations and/or days of disability in patients with chronic bronchitis or chronic obstructive pulmonary disease. Secondary objectives • To assess whether Mucolytics lead to improvement in lung function or quality of life. • To determine frequency of adverse effects associated with use of Mucolytics. Search methods We searched the Cochrane Airways Group Specialised Register and reference lists of articles on 10 separate occasions, most recently in July 2014. Selection criteria We included randomised studies that compared oral Mucolytic therapy versus placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. Data collection and analysis This review analysed summary data only, most derived from published studies. For earlier versions, one review author extracted data, which were rechecked in subsequent updates. In later versions, review authors double-checked extracted data and then entered data into RevMan for analysis. Main results We added four studies for the 2014 update. The review now includes 34 trials, recruiting a total of 9367 participants. Many studies did not clearly describe allocation concealment; hence selection bias may have inflated the results, which reduces our confidence in the findings. Results of 26 studies with 6233 participants show that the likelihood that a patient could be exacerbation-free during the study period was greater among Mucolytic groups (Peto odds ratio (OR) 1.75, 95% confidence interval (CI) 1.57 to 1.94). However, more recent studies show less benefit of treatment than was reported in earlier studies in this review. The overall number needed to treat with Mucolytics for an additional beneficial outcome for an average of 10 months - to keep an additional participant free from exacerbations - was eight (NNTB 8, 95% CI 7 to 10). Use of Mucolytics was associated with a reduction of 0.03 exacerbations per participant per month (mean difference (MD) -0.03, 95% CI -0.04 to -0.03; participants = 7164; studies = 28; I2 = 85%) compared with placebo, that is, about 0.36 per year, or one exacerbation every three years. Very high heterogeneity was noted for this outcome, so results need to be interpreted with caution. The type or dose of Mucolytic did not seem to alter the effect size, nor did the severity of COPD, including exacerbation history. Longer studies showed smaller effects of Mucolytics than were reported in shorter studies. Mucolytic use was associated with a reduction of 0.43 days of disability per participant per month compared with placebo (95% CI -0.56 to -0.30; studies = 13; I2 = 61%). With Mucolytics, the number of people with one or more hospitalisations was reduced, but study results were not consistent (Peto OR 0.68, 95% CI 0.52 to 0.89; participants = 1788; studies = 4; I2 = 58%). Investigators reported improved quality of life with Mucolytics (MD -2.64, 95% CI -5.21 to -0.08; participants = 2231; studies = 5; I2 = 51%). Although this mean difference did not reach the minimal clinically important difference of -4 units, we cannot assess the population impact, as we do not have the data needed to carry out a responder analysis. Mucolytic treatment was not associated with any significant increase in the total number of adverse effects, including mortality (Peto OR 1.03, 95% CI 0.52 to 2.03; participants = 2931; studies = 8; I2 = 0%), but the confidence interval is too wide to confirm that the treatment has no effect on mortality. Authors' conclusions In participants with chronic bronchitis or COPD, we are moderately confident that treatment with Mucolytics may produce a small reduction in acute exacerbations and a small effect on overall quality of life. Our confidence in the results is reduced by the fact that effects on exacerbations shown in early trials were larger than those reported by more recent studies, possibly because the earlier smaller trials were at greater risk of selection or publication bias, thus benefits of treatment may not be as great as was suggested by previous evidence.

  • Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
    The Cochrane database of systematic reviews, 2012
    Co-Authors: Phillippa Poole, Peter N. Black, Christopher J Cates
    Abstract:

    Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume or purulence of sputum, or both. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference among countries in terms of prescribing of Mucolytics depending on whether or not they are perceived to be effective. to determine if treatment with Mucolytics reduces the frequency of exacerbations, days of disability, or both, in participants with chronic bronchitis or chronic obstructive pulmonary disease, or both. to determine if Mucolytics lead to an improvement in lung function or quality of life and to determine the frequency of adverse effects associated with Mucolytics. We searched the Cochrane Airways Group Specialised Register and reference lists of articles on ten separate occasions, the most recent being in July 2012. We included randomised studies that compared oral Mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. We excluded studies of people with asthma and cystic fibrosis. The review analysed summary data only, the majority from published studies. For earlier versions, one author extracted data, which was rechecked in subsequent updates. In later versions, we double-checked data extraction. We then entered data into RevMan for analysis. Two further trials have been added to the review for the 2012 update. There are now 30 trials in the review, recruiting a total of 7436 participants. Allocation concealment was not clearly described in the early trials, and selection bias may have inflated the results, which reduces our confidence in the findings of these trials.The likelihood of being exacerbation-free during the study period (22 trials in 4886 participants with a mean duration of 10 months) was greater in the Mucolytic group for the double-blind trials (Peto odds ratio (OR) 1.84; 95% confidence interval (CI) 1.63 to 2.07). However, the more recent trials show less benefit of treatment than the earlier trials included in this review. The overall number needed to treat with Mucolytics to keep an additional participant free from exacerbations over 10 months was seven (NNTB 7; 95% CI 6 to 9). The use of Mucolytics was associated with a reduction of 0.04 exacerbations per participant per month (95% CI -0.04 to -0.03) compared with placebo; that is about 0.48 per year, or one exacerbation every two years. There was very high heterogeneity in this outcome (I(2) = 87%) so results need to be interpreted with caution.The number of days of disability per month also fell (mean difference (MD) -0.48; 95% CI -0.65 to -0.30) in 12 trials on 2305 participants. There was no clinically important improvement in lung function or consistent impact on quality of life with Mucolytics. Mucolytic treatment was not associated with any significant increase in adverse effects, including mortality (Peto OR 0.75; 95% CI 0.35 to 1.64) in six trials on 1821 participants. In participants with chronic bronchitis or COPD, treatment with a Mucolytic may produce a small reduction in acute exacerbations, but may have little or no effect on the overall quality of life. The effects on exacerbations shown in early trials were larger than those found in the more recent studies. This may be because the earlier smaller trials were at higher risk of selection or publication bias, so the benefits of treatment may not be as large as suggested by the previous evidence.

Krishna Pillai - One of the best experts on this subject based on the ideXlab platform.

  • assessment of a novel Mucolytic solution for dissolving mucus in pseudomyxoma peritonei an ex vivo and in vitro study
    Pleura and peritoneum, 2017
    Co-Authors: Krishna Pillai, Javed Akhter, David L. Morris
    Abstract:

    Background Pseudomyxoma peritonei (PMP) is difficult to treat. Intraperitoneal delivery of Mucolytic solutions might potentially improve therapy, in addition to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy. Methods Comparison of Mucolytic effect of two formulations (control: bromelain 300 µg/mL+N-Acetylcystein 250 mM; test: bromelain 200 µg/mL+200 mM cysteamine) in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 PMP patients. Mucin plugs were classified according to their density into three categories: hard, semi hard and soft. Simulation of peritoneal washing ex vivo using a closed heated circulating pump. Results Solubilisation was faster with the test vs. the control formulation (90 vs. 180 min) for dissolving the soft mucin plugs (p < 0.05). The test solution was also more effective in dissolving the hard mucus plugs compared to control (82.5±2.74 % vs. 36.33±3.27 %). All mucin types disintegrated in simulated peritoneal washing. Cytotoxicity of the test solution on HT29 cell line was time-dependent. Conclusions The test formulation is more effective and faster than the control formulation in dissolving mucus plugs of various densities. Mucus plugs were all solubilised after 40 min in simulated peritoneal washing. This novel Mucolytic formulation might pave the way for an effective and less invasive therapy of PMP in the future.

  • Assessment of a novel Mucolytic solution for dissolving mucus in pseudomyxoma peritonei: an ex vivo and in vitro study.
    Pleura and peritoneum, 2017
    Co-Authors: Krishna Pillai, Javed Akhter, David L. Morris
    Abstract:

    Background Pseudomyxoma peritonei (PMP) is difficult to treat. Intraperitoneal delivery of Mucolytic solutions might potentially improve therapy, in addition to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy. Methods Comparison of Mucolytic effect of two formulations (control: bromelain 300 µg/mL+N-Acetylcystein 250 mM; test: bromelain 200 µg/mL+200 mM cysteamine) in vitro on a mucin producing cell lines (HT29) and ex vivo on mucus obtained from 18 PMP patients. Mucin plugs were classified according to their density into three categories: hard, semi hard and soft. Simulation of peritoneal washing ex vivo using a closed heated circulating pump. Results Solubilisation was faster with the test vs. the control formulation (90 vs. 180 min) for dissolving the soft mucin plugs (p 

  • Efficacy of a novel Mucolytic agent on pseudomyxoma peritonei mucin, with potential for treatment through peritoneal catheters.
    American journal of cancer research, 2014
    Co-Authors: Javed Akhter, Krishna Pillai, Terence C. Chua, Naeef Alzarin, David L. Morris
    Abstract:

    Compared to current treatment for pseudomyxoma peritonei (PMP), the extraction of solubilised mucin through peritoneal catheter can be minimally invasive. However, mucin has variable appearance that may influence mucolysis. Hence, we investigated the mucolysis of 36 mucin samples with a novel agent. Using visual inspection and hardness index, PMP mucin was classified into three grades. The mucin pathological category was identified from patient record. Subsequently, the dissolution of the samples was tested. For in vitro, 1 g of mucin was treated to the Mucolytic agent in 10 ml TRIS buffer at 37 deg. Celsius for 3 hours, with weighing of residual mucin. Control treatment was similar but received TRIS buffer. For in vivo, 2 g of implanted intra-peritoneal mucin in nude rats was treated to Mucolytic (2 X 500 ul/24 hr, over 48 hours, plus another treatment before sacrifice at 56 hours, with weighing of residual mucin. Controls were treated but only with TRIS buffer. Six animals were used for each mucin grade (3 Mucolytic treated & and 3 controls). Grades of mucin were soft mucin (62%), semi hard (20%) and hard mucin (18%). Diffuse peritoneal adenomucinosis had 50% of soft mucin and peritoneal mucinous carcinoma had 11% (P = 0.0382). In vitro and in vivo absolute disintegration was 100% for soft, 57.38% and 48.67% for semi hard, 50% and 28.67% for hard mucin. Majority of mucin were soft with complete disintegration, the rest showed variable disintegration, suggesting that the Mucolytic has potential for treating PMP.

  • Potential Mucolytic agents for mucinous ascites from pseudomyxoma peritonei.
    Investigational new drugs, 2012
    Co-Authors: Krishna Pillai, Javed Akhter, Terence C. Chua, David L. Morris
    Abstract:

    Pseudomyxoma peritonei is a disease characterised by the accumulation of mucinous ascites. Thus far, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be effective at eradicating disease. Chemotherapy has been less effective, providing disease stabilization but not demonstrating significant treatment responses. Mucolytic is a potential class of drug that may be exploited in the chemical management of this disease. A variety of potential Mucolytic agents are explored in this review providing evidence of basic biochemical evidence of its efficacy with potential translational application.