The impact of alpha-1 antitrypsin augmentation therapy on neutrophil-driven respiratory disease in deficient individuals

Management of lung disease in patients with alpha-1 antitrypsin deficiency (AATD) includes both non-pharmacological and pharmacological approaches. Lifestyle changes with avoidance of environmental pollutants, including tobacco smoke, improving exercise levels and nutritional status, all encompassed under a disease management program, are crucial pillars of AATD management. Non-pharmacological therapies follow conventional treatment guidelines for chronic obstructive pulmonary disease. Specific pharmacological treatment consists of administering exogenous alpha-1 antitrypsin (AAT) protein intravenously (augmentation therapy). This intervention raises AAT levels in serum and lung epithelial lining fluid, increases anti-elastase capacity, and decreases several inflammatory mediators in the lung. Radiologically, augmentation therapy reduces lung density loss over time, thus delaying disease progression. The effect of augmentation therapy on other lung-related outcomes, such as exacerbation frequency/length, quality of life, lung function decline, and mortality, are less clear and questions regarding dose optimization or route of administration are still debatable. This review discusses the rationale and available evidence for these interventions in AATD.

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Economics of respiratory disease in dairy replacement heifers

Animal Health Research Reviews ◽

10.1017/s1466252320000250 ◽

2020 ◽

Vol 21 (2) ◽

pp. 143-148

Author(s):

Michael W. Overton

Keyword(s):

Respiratory Disease ◽

Milk Production ◽

Incident Case ◽

Data Set ◽

Dairy Heifers ◽

The Usa ◽

History Of ◽

On Farm ◽

The Impact ◽

Selective Culling

AbstractBovine respiratory disease (BRD) is a frequent disease concern in dairy cattle and is most commonly diagnosed in young dairy heifers. The impact of BRD is highly variable, depending on the accuracy and completeness of detection, effectiveness of treatment, and on-farm culling practices. Consequences include decreased rate of weight gain, a higher culling risk either as heifers or as cows, delayed age at first service, delayed age at first calving, and in some cases, lower future milk production. In this data set of 104,100 dairy replacement heifers from across the USA, 36.6% had one or more cases diagnosed within the first 120 days of age with the highest risk of new cases occurring prior to weaning. Comparison of the raising cost for heifers with BRD and those without a recorded history of BRD resulted in an estimated cost per incident case occurring in the first 120 days of age of $252 or $282, depending upon whether anticipated future milk production differences were considered or not. Current market conditions contributed to a cost estimate that is significantly higher than previously published estimates, driven in part by the losses associated with selective culling of a subset of heifers that experienced BRD.

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Anti-Proteases and Alpha-1 Antitrypsin Augmentation Therapy

Respiratory Care ◽

10.4187/respcare.05933 ◽

2018 ◽

Vol 63 (6) ◽

pp. 690-698 ◽

Cited By ~ 6

Author(s):

Charlie Strange

Keyword(s):

Augmentation Therapy ◽

Alpha 1 Antitrypsin

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Quantifying the impact of current and future concentrations of air pollutants on respiratory disease risk in England

Environmental Health ◽

10.1186/s12940-017-0237-1 ◽

2017 ◽

Vol 16 (1) ◽

Cited By ~ 13

Author(s):

Francesca Pannullo ◽

Duncan Lee ◽

Lucy Neal ◽

Mohit Dalvi ◽

Paul Agnew ◽

...

Keyword(s):

Respiratory Disease ◽

Air Pollutants ◽

Disease Risk ◽

The Impact

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Lungworms (Metastrongylus Spp.) Demonstrated in Domestic Pigs with Respiratory Disease - What was the True Relevance of that?

10.21203/rs.3.rs-1188679/v1 ◽

2021 ◽

Author(s):

Per Wallgren ◽

Emelie Pettersson

Keyword(s):

Respiratory Disease ◽

Pasteurella Multocida ◽

Ascaris Suum ◽

Clinical Signs ◽

Mycoplasma Hyopneumoniae ◽

Disease Outbreak ◽

Domestic Pigs ◽

Faecal Samples ◽

Routine Inspection ◽

The Impact

Abstract BackgroundAn outdoor pig herd was affected by severe respiratory disease in one out of three pastures. At necropsy, Mycoplasma hyopneumoniae and Pasteurella multocida were detected in the lungs, as well as the lung worm Metastrongylus apri. The life cycle of Metastrongylus spp. includes earth worms as an intermediate host, and since domesticated pigs mainly are reared indoors lungworms has not been diagnosed in domestic pigs in Sweden for decades, not even in pigs reared outdoors. Therefore, this disease outbreak was scrutinised from the view of validating the impact of Metastrongylus spp..ResultsAt the time of the disease outbreak, neither eggs of Metastrongylus spp. nor Ascaris suum were detected in faeces of pigs aged ten weeks. In contrast, five-months-old pigs at the pasture with respiratory disease shed large amounts of eggs from Ascaris suum, whereas Ascaris suum not was demonstrated in healthy pigs aged six months at another pasture. Low numbers of eggs from Metastrongylus spp. were seen in faecal samples from both these age categories.At slaughter, seven weeks later, ten normal weighted pigs in the preceding healthy batch were compared with ten normal weighted and five small pigs from the affected batch. Healing Mycoplasma-like pneumonic lesions were seen in all groups. Small pigs had more white spot liver lesions, and all small pigs shed eggs of Ascaris suum in faeces, compared to around 50% of the pigs in the normally sized groups. Metastrongylus spp. were demonstrated in 13 of the 25 pigs (52%), %), representing all groups included.ConclusionAs Metastrongylus spp. were demonstrated regardless of health status, and in another healthy outdoor herd, the impact of Metastrongylus spp. on the outbreak of respiratory disease was depreciated. Instead, Metastrongylus spp. was suggested to be common in outdoor production, although rarely diagnosed. The reason for this is because they will escape detection at routine inspection at slaughterhouses, and that they appeared to generally not induce clinical signs of respiratory disease. Instead, a possible association with a high burden of Ascaris suum was suggested to have preceded the severe outbreak with respiratory disease.

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Investigating the discriminative value of Early Warning Scores in patients with respiratory disease using a retrospective cohort analysis of admissions to Nottingham University Hospitals Trust over a 2-year period

BMJ Open ◽

10.1136/bmjopen-2017-020269 ◽

2018 ◽

Vol 8 (7) ◽

pp. e020269 ◽

Cited By ~ 3

Author(s):

Sarah Forster ◽

Gemma Housley ◽

Tricia M McKeever ◽

Dominick E Shaw

Keyword(s):

Respiratory Disease ◽

Early Warning ◽

Retrospective Cohort ◽

Cohort Analysis ◽

Scoring Systems ◽

University Hospitals ◽

Retrospective Cohort Analysis ◽

Early Warning Scores ◽

The Impact ◽

Higher Sensitivity

ObjectiveEarly Warning Scores (EWSs) are used to monitor patients for signs of imminent deterioration. Although used in respiratory disease, EWSs have not been well studied in this population, despite the underlying cardiopulmonary pathophysiology often present. We examined the performance of two scoring systems in patients with respiratory disease.DesignRetrospective cohort analysis of vital signs observations of all patients admitted to a respiratory unit over a 2-year period. Scores were linked to outcome data to establish the performance of the National EWS (NEWS) compared results to a locally adapted EWS.SettingNottingham University Hospitals National Health Service Trust respiratory wards. Data were collected from an integrated electronic observation and task allocation system employing a local EWS, also generating mandatory referrals to clinical staff at set scoring thresholds.Outcome measuresProjected workload, and sensitivity and specificity of the scores in predicting mortality based on outcome within 24 hours of a score being recorded.Results8812 individual patient episodes occurred during the study period. Overall, mortality was 5.9%. Applying NEWS retrospectively (vs local EWS) generated an eightfold increase in mandatory escalations, but had higher sensitivity in predicting mortality at the protocol cut points.ConclusionsThis study highlights issues surrounding use of scoring systems in patients with respiratory disease. NEWS demonstrated higher sensitivity for predicting death within 24 hours, offset by reduced specificity. The consequent workload generated may compromise the ability of the clinical team to respond to patients needing immediate input. The locally adapted EWS has higher specificity but lower sensitivity. Statistical evaluation suggests this may lead to missed opportunities for intervention, however, this does not account for clinical concern independent of the scores, nor ability to respond to alerts based on workload. Further research into the role of warning scores and the impact of chronic pathophysiology is urgently needed.

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