Aging as a consequence of misrepair -- A novel theory of aging

It is now increasingly realized that the underlying mechanisms which govern aging is a complex interplay of genetic regulation and damage accumulation. Aging as a result of accumulation of ‘faults’ on cellular and molecular levels, has been proposed in the damage (fault)-accumulation theory by Kirkwood 2006. However, this theory fails to explain some aging phenotypes such as fibrosis and premature aging, since terms such as ‘damage’ and ‘fault’ are not specified. Therefore we introduce here a specification of the underlying mechanism of aging and arrive at a novel theory: aging of the body is a result of the accumulation of Misrepair of tissue. It emphasizes: a) it is Misrepair, not the original damage, that accumulates and leads to aging; and b) aging can occur at different levels, however aging of the body takes place at least on the tissue level, but not necessarily on cellular/molecular level. The novel concept of Misrepair introduced here unifies the understanding of the roles of environmental damage, repair, gene regulation, and multicellular structure in the aging process. The Misrepair-accumulation theory introduced in the present paper gives explanations for the aging phenotypes, premature aging, and the difference of longevity in different species, and is consistent with the point of view of physical theory of complex systems

New and emerging technologies for the diagnosis and monitoring of chronic obstructive pulmonary disease: a horizon scanning review

There is a need for straightforward, novel diagnostic and monitoring technologies to enable the early diagnosis of COPD and its differentiation from other respiratory diseases, to establish the cause of acute exacerbations and to monitor disease progression. We sought to establish whether technologies already in development could potentially address these needs. A systematic horizon scanning review was undertaken to identify technologies in development from a wide range of commercial and non-commercial sources. Technologies were restricted to those likely to be available within 18 months, and then evaluated for degree of innovation, potential for impact, acceptability to users and likelihood of adoption by clinicians and patients with COPD. Eighty technologies were identified, of which 25 were considered particularly promising. Biomarker tests, particularly those using sputum or saliva samples and/or available at the point of care, were positively evaluated, with many offering novel approaches to early diagnosis and to determining the cause for acute exacerbations. Several wrist-worn devices and smartphone-based spirometers offering the facility for self-monitoring and early detection of exacerbations were also considered promising. The most promising identified technologies have the potential to improve COPD care and patient outcomes. Further research and evaluation activities should be focused on these technologies

Early respiratory diagnosis: benefits of enhanced lung function assessment.

INTRODUCTION: The National Health Service for England Long Term Plan identifies respiratory disease as one of its priority workstreams. To assist with earlier and more accurate diagnosis of lung disease they recommend improvement in delivery of quality-assured spirometry. However, there is a likelihood that patients will present with abnormal gas exchange when spirometry results are normal and therefore there will be a proportion of patients whose time to diagnosis is still protracted. We wished to determine the incidence rate of this occurring within our Trust. METHODS: A retrospective review of all patients attending the lung function laboratory for their first pulmonary function assessment from June 2006 to December 2020 was undertaken. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) >-1.64 standardised residual (SR) was used to confirm no obstructive lung function abnormality and FVC >-1.64 SR to confirm no suggestion of a restrictive lung function abnormality. Lung gas transfer for carbon monoxide (TLCO) and transfer coefficient of the lung for carbon monoxide (KCO) <-1.64 SR confirmed the presence of a gas exchange abnormality. Spirometry and gas transfer reference values generated by the Global Lung Initiative were used to determine normality. RESULTS: Of 12 835 eligible first visits with normal FEV1/FVC and FVC, 4856 (37.8%) were identified as having an abnormally low TLCO and 3302 (25.7%) presenting with an abnormally low KCO. Of 3494 with FEV1/FVC SR <-1.64, 3316 also had a ratio of <0.70, meaning 178 (5%) of patients in this cohort would have been misclassified as having obstructive lung disease using the 0.70 cut-off recommended by the Global Initiative for Chronic Obstructive Lung Disease for diagnosing obstructive lung disease. DISCUSSION: In conclusion, to assist with ensuring more accurate and timely diagnosis of lung disease and enhance patients' diagnostic pathway, we recommend the performance of lung gas transfer measurements alongside spirometry in all healthcare settings. To assess and monitor gas transfer at the earliest opportunity we recommend this is implemented into new models being developed within community hubs. This will increase the identification of lung function abnormalities and provide patients with a definitive diagnosis earlier

Lung function improvements in emphysema following pneumonia.

We describe two cases of patients with emphysema who, in the lead up to hyperinflation intervention, developed pneumonia with significant physiological, anatomical, functional and quality of life improvement observed following. This directly goes against the natural history of both disease processes, demonstrating the benefit resulting from infective autobullectomy

Associations between the psychological health of patients and carers in advanced COPD

Objective: Anxiety and depression are highly prevalent in patients with chronic obstructive pulmonary disease (COPD) and their informal carers, and associated with numerous risk factors. However, few studies have investigated these in primary care or the link between patient and carer anxiety and depression. We aimed to determine this association, and factors associated with anxiety and depression in patients, carers, and both in a dyad, in a population-based sample. Methods: Prospective, cross-sectional analysis of data from 119 advanced COPD patients and their carers. Patient and carer scores ≥8 on the Hospital Anxiety and Depression Scale were defined as cases of anxiety and depression; Chi-square, independent-t and Mann-Whitney U tests were used to determine variables significantly associated with these. Patient-carer dyads were categorised into four groups relating to the presence of anxiety or depression: (1) in both the patient and carer, (2) patient only, (3) carer only and (4) neither; factors associated with dyad anxiety or depression were determined with Chi-square, one-way ANOVA and Kruskal-Wallis tests. Results: Prevalence of anxiety and depression was 46.4% (n=52) and 42.9% (n=48) in patients, and 46.0% (n=52) and 23.0% (n=26) in carers, respectively. Patient and carer anxiety and depression were significantly associated. Patient anxiety and depression was also significantly associated with younger age, more physical co-morbidities, more exacerbations, greater dyspnoea, greater fatigue, and poor mastery. Carer anxiety and depression was significantly associated with younger age, being female and separated/divorced/widowed, higher educational level, more physical co-morbidities, unmet support needs, greater subjective caring burden and poor patient mastery. Dyad anxiety or depression was significantly associated with greater patient fatigue. Conclusion: Anxiety and depression of patients and carers are associated. Dyad anxiety or depression was associated with greater patient fatigue. It is necessary to identify and address patient, carer and dyad psychological morbidity in advanced COPD

Do patients and carers agree on symptom burden in advanced COPD?

OBJECTIVE: Accurate informal carer assessment of patient symptoms is likely to be valuable for decision making in managing the high symptom burden of COPD in the home setting. Few studies have investigated agreement between patients and carers in COPD. We aimed to assess agreement between patients and carers on symptoms, and factors associated with disagreement in a population-based sample of patients with advanced COPD. PATIENTS AND METHODS: This was a prospective, cross-sectional analysis of data from 119 advanced COPD patients and their carers. Patients and carers separately rated symptoms on a 4-point scale. Wilcoxon signed-rank tests and weighted Cohen's kappa determined differences in patient and carer scores and patient-carer agreement, respectively. We identified characteristics associated with incongruence using Spearman's rank correlation and Mann-Whitney U tests. RESULTS: There were no significant differences between group-level patient and carer scores for any symptom. Patient-carer individual-level agreement was moderate for constipation (k=0.423), just below moderate for diarrhea (k=0.393) and fair for depression (k=0.341), fatigue (k=0.294), anxiety (k=0.289) and breathlessness (k=0.210). Estimation of greater patient symptom burden by carers relative to patients themselves was associated with non-spousal patient-carer relationship, non-cohabitating patients and carers, carer symptoms of anxiety and depression and more carer unmet support needs. Greater symptom burden estimation by the patient relative to the carer was associated with younger patients and longer duration of COPD. CONCLUSION: Overall, agreement between patients and carers was fair to moderate and was poorer for more subjective symptoms. There is a need to encourage open dialogue between patients and carers to promote shared understanding, help patients express themselves and encourage carers to draw attention to symptoms that patients do not report. The findings suggest a need to screen for and address both the psychological morbidities in patients with advanced COPD and their carers and unmet support needs in carers