Table 2 - available via license: Creative Commons Attribution-NonCommercial 4.0 International
Content may be subject to copyright.
Source publication
Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease (COPD), although factors influencing the length and frequency of each episode are poorly understood. This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin (AAT) deficiency (PiZ phenotype) and COPD....
Contexts in source publication
Context 1
... the 23 patients, one recorded no treated exacerba- tion and one had an excessive number (more than 10 in a year), which represented a clear outlier. For the remaining 21 patients, there was a significant nega- tive correlation between corrected gas transfer (KCO% predicted) and frequency of treated episodes (Table 2 and Figure 2). No other baseline characteristic, includ- ing baseline PD15, was related to frequency of treated episodes. ...
Context 2
... likelihood of an episode being treated correlated negatively with FEV 1 % predicted and the FEV 1 /forced vital capacity (FVC) ratio (Table 2). Other factors shown to affect the rate of treated episodes were the number of major symp- toms outlined by Anthonisen et al, 35 presence of cold-like symptoms, chest pain, and nocturnal symptoms as previ- ously published 37 (Chi-square, P , 0.001 for all). ...
Context 3
... mean (±standard error) total length of exacerbation, delay in initiation of antibiotic treatment, and resolution of all symptoms after the start of antibiotic therapy (61 antibiotic- treated episodes in 17 patients) were 17.5 ± 1.9, 4.4 ± 0.5, and 12.9 ± 1.8 days, respectively. Of the 61 episodes treated with antibiotics, the exacerba- tion length was greater the longer the delay in initiation of treatment (Table 2). This relationship was stronger when epi- sodes also treated with steroids were excluded (49 episodes in 15 patients; Table 2 and Figure 3). ...
Context 4
... the 61 episodes treated with antibiotics, the exacerba- tion length was greater the longer the delay in initiation of treatment (Table 2). This relationship was stronger when epi- sodes also treated with steroids were excluded (49 episodes in 15 patients; Table 2 and Figure 3). ...
Context 5
... length of any treated episode was related to Anthonisen criteria, with type 1 exacerbations lasting longer than type 2, which in turn were longer than type 3 (P = 0.001). However, the average length for all treated episodes corre- lated negatively with the PD15, with longer episodes relating to lower lung density (Table 2). When analyzed using the linear regression stepwise model, the number of Anthonisen symptoms was the best independent predictor of length of any treated episode. ...
Context 6
... delay in commencing treatment was shorter in patients with lower absolute FEV 1 , FEV 1 /FVC ratio, and PD15 at baseline (r = 0.272, P = 0.036, r = 0.461, P , 0.001, and r = 0.786, P , 0.001; Table 2) and with a higher symptom score on day 1 (r = −0.368, P = 0.004). ...
Context 7
... was a significant negative correlation between symp- tom score on day 1 and baseline FEV 1 , FEV 1 /VC%, and lung density (81 episodes; Table 2). No relationship was found with KCO. ...
Context 8
... of symptoms after the start of antibiotic treatment was not affected by delay in the start of therapy. However, there was a significant negative correlation between resolution and KCO% predicted (Table 2 and Figure 5). No other factor affected resolution time following initiation of treatment. ...
Similar publications
Background
Generally, alpha-1 antitrypsin deficiency (AATD) is suspected in young patients with pulmonary emphysema or chronic obstructive pulmonary disease (COPD). Patients often suffer from diagnostic gaps and are misdiagnosed with chronic obstructive pulmonary disease (COPD), asthma, and airway hyperresponsiveness (AHR), as AATD may present with...
Purpose
Alpha-1 antitrypsin deficiency is associated with the development of chronic obstructive pulmonary disease (COPD), whereas increased levels of serum alpha-1antitrypsin occur in response to inflammation. The effects of alpha-1 antitrypsin levels on the clinical course of COPD had been unclear. We investigated the association of serum alpha-1...
Background
Generic measures of health-related quality of life (HRQoL), such as the 36-Item Short Form Survey (SF-36), are widely used in assessing chronic conditions. These tools have an advantage over disease-specific instruments, as they allow comparisons across different health conditions and with the general population. In alpha-1 antitrypsin d...
Alpha 1 antitrypsin deficiency (AATD) is a rare cause of chronic obstructive pulmonary disease. The lung disease is thought to be caused primarily by a lack of effective protection against the harmful effects of neutrophil elastase due to the low AAT levels in the lung. Patients may also develop liver disease due to polymerisation of AAT within hep...
During the COVID-19 pandemic the number of hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations was significantly reduced. The reason for this decline is not fully understood. Governmental non-pharmaceutical interventions (NPI’s), an increase in community treated exacerbations, or healthcare avoidance by patients, a...
Citations
... This rate is almost identical to the findings by Vijayasaratha et al of type-1 exacerbations (worsening of all 3 symptoms), accounting for 34% of total exacerbations in a cohort of patients with AATD COPD. 23,24 In our study, approximately 75% of the symptom events with all 3 of the above respiratory symptoms were identified by the better understanding the symptom-based definition of pulmonary exacerbations from the patients' perspective. ...
Rationale:
Identifying pulmonary exacerbations in patients with alpha-1 antitrypsin deficiency (AATD) is critical as they are associated with disease progression and poor health-related quality of life. Not all changes in usual respiratory symptoms will be identified as exacerbations by patients with AATD.
Methods:
Data collected via regular monthly telephone calls during the first year of the AlphaNet Step Forward Study were analyzed. AlphaNet subscribers were asked about changes in their usual respiratory symptoms, whether they considered changes in symptoms to be pulmonary exacerbations, and their management. Participants who reported changes in their usual respiratory symptoms throughout the year were included in the study. Per-patient and per-event analyses were performed.
Results:
Participants (n=316, age 58±10 years, 53% female) reported 797 events of changes in their usual respiratory symptoms in one year. Almost half (48%) of these symptom events were identified as pulmonary exacerbations by the study participants. The average number of symptoms was higher in events recognized by participants as exacerbations than those not identified as exacerbations (3.3±1.5 vs. 1.8±1.1, respectively). A greater proportion of the exacerbation events were managed by taking antibiotics or corticosteroids or both (81%, 53%, and 41% of the events, respectively). With exacerbations, participants mainly spoke to the pulmonary specialist (39%) or went to the doctor's office (37%). Symptom events not recognized as exacerbations were mostly self-treated (56%).
Conclusions:
Changes in usual pulmonary symptoms are not universally recognized as exacerbations. Patients' perspectives in recognizing changes in pulmonary symptoms as exacerbation events are critical.
... In the acute management of disease exacerbations, early antibiotic use has been shown to decrease exacerbation length in patients with AATD. 47 What we do not know Although no specific RCT exists for patients with AATD and COPD, all other beneficial studies in COPD are widely used to guide recommendations for the management of AATD. These interventions include the use of long-acting muscarinic antagonists, the continuous or intermittent use of antibiotics to prevent or reduce COPD exacerbations, 48,49 mucolytics to reduce exacerbations, 50 the use of supplemental oxygen in subjects with severe hypoxemia (partial pressure of oxygen <55 mmHg), 51 and the use of ICS in patients with frequent exacerbations and eosinophilia. ...
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.
... 78 Anthonisen criteria has also been demonstrated to relate to exacerbation duration in AATD, with type 1 exacerbations lasting longer than type 2 exacerbations, which were longer than type 3 (p = 0.001). 79 Untreated exacerbations in AATD are estimated to contribute to 48% of total exacerbations, similar to rates seen in usual COPD. 7,80 Patients perception of unwellness and breathlessness was significantly shorter in untreated versus treated AATD exacerbations, by approximately 80% and 50% respectively, implicating their role in patients' decisions to seek additional treatment. ...
... 7 Cold-like symptoms were reported in approximately one third of AATD COPD exacerbations and coryzal illness was reported as the best independent predictive factor of AATD patients seeking treatment (p = 0.001) according to regression analysis. 7,79 This may relate to the observation that cold-like symptoms during exacerbations of usual COPD relate to significantly greater falls in FEV1 (p = 0.043), compared to exacerbations without such features. 20 Upper-respiratory tract symptoms at exacerbation are considered to be associated with viral infections, with higher HRV loads detected in patients with cold-like symptoms or sore throats than those without (p = 0.046 and p = 0.006, respectively). ...
... 4,78,86 In a cohort of 87 AATD COPD subjects, the proportion of patients experiencing exacerbations each year was consistent across three-year period, although whether individual exacerbation rates remained consistent was not reported. 79 Patients experiencing exacerbations in year one were more likely to continue having exacerbations in the second and third year (p = 0.04 and p < 0.001, respectively). 79 The demographics and clinical characteristics of frequent exacerbators in AATD, and the influence of specific COPD phenotypes (e.g. ...
Alpha-1 antitrypsin deficiency (AATD) is an important risk factor for development of chronic obstructive pulmonary disease (COPD). Patients with AATD classically develop a different pattern of lung disease from those with usual COPD, decline faster and exhibit a range of differences in pathogenesis, all of which may be relevant to phenotype and/or impact of exacerbations. There are a number of definitions of exacerbation, with the main features being worsening of symptoms over at least 2 days, which may be associated with a change in treatment. In this article we review the literature surrounding exacerbations in AATD, focussing in particular on ways in which they may differ from such events in usual COPD, and the potential impact on clinical management.
... 49 Younger patients may differ from older patients with COPD in their disease pathology and natural history. 50 The majority of COPD patients are over 45 years. The cut off of 31 March 2009 for index cases was set so that any admissions in the subsequent year, up to and including 31 March 2010, of each patient so identified would be included in the data set. ...
Chronic lung disease:
LOWER RISK OF READMISSION FOR LONDON-BASED PATIENTS: A managed reduction of hospital readmissions for London-based chronic lung disease patients may not be needed. Preventing hospital readmissions for patients with chronic obstructive pulmonary disease (COPD) is a key priority to improve patient care and limit costs. However, few data are available to determine and ultimately reduce the risk of readmission. Timothy Harries at King's College, London, and co-workers conducted a longitudinal study incorporating all COPD admissions into UK hospitals for 20,932 patients registered at London general practitioners between 2006 and 2010. They found that 32% of patients were readmitted within a year, 17.8% within 90 days and 10% within 30 days. Neither age nor geographical deprivation were useful predictors of readmission. These represent lower than estimated levels of readmission, suggesting there may be fewer opportunities to reduce the risk of readmission further.
... In the lung, AAT protects lung parenchymal tissue from proteolytic damage, in particular by proteases released by inflammatory cells such as neutrophil elastase [9][10][11]. The resulting protease/ antiprotease imbalance in AAT deficiency (AATD), often leads to early-onset COPD and accelerated emphysema progression, which highlights the importance of early diagnosis in order to apply impactful preventive and therapeutic interventions [12]. Overall, it is estimated that 1-2% of all COPD patients have severe AATD [9] with up to 10% exhibiting some level of protein deficiency [9,13]. ...
... There is significant underrecognition of both COPD and AATD as a cause of COPD. COPD is underrecognized particularly during its early stages with different assessments estimating that at least 50% of symptomatic COPD patients remain undetected [12,14,15]. Although COPD affects up to 10% of patients in the general population in the USA, the clinic prevalence reported by general practitioners is less than 2% [16]. ...
... Although COPD affects up to 10% of patients in the general population in the USA, the clinic prevalence reported by general practitioners is less than 2% [16]. AATD as a cause of COPD is also rarely considered, with up to 95% of symptomatic individuals not being properly identified [12,14,15,17]. Primary care physicians are in a key position to improve these dire estimates as they are the healthcare providers who will likely interact with these patients first, and are therefore in a unique position to significantly impact the care of these patients [18,19]. ...
Objective: Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder that can cause chronic obstructive pulmonary disease (COPD) and liver cirrhosis, two clinical conditions commonly seen by primary care physicians. AATD is estimated to affect 1/4000–1/5000 people in the United States and 1–2% of all COPD cases.
Methods: PubMed was searched for relevant articles using AAT/AATD-related terms.
Results: Unfortunately, <10% of symptomatic individuals have been properly diagnosed primarily due to the underdiagnosis of COPD and the lack of awareness of AATD as a possible underlying cause. Because primary care providers are most likely to be the first to encounter symptomatic individuals, their role in the identification and early diagnosis of AATD patients is instrumental, particularly since therapy to slow lung disease progression is available. The diagnosis of AATD is laboratory-based rather than clinical. Testing for AATD should be part of the reflex testing that follows any COPD diagnosis or unexplained liver disease and can be performed by determining the AAT phenotype or genotype along with serum AAT levels. Both nonpharmacological and pharmacological approaches are recommended for treatment of lung disease, including smoking cessation, bronchodilators or supplemental oxygen as needed. Specific augmentation of AAT levels with regular purified AAT infusions has been found to slow lung function decline and emphysema progression in patients with moderate airflow obstruction and severely low serum AAT levels.
Conclusions: Improving primary care provider awareness and promoting regular reflex testing all COPD patients for AATD may significantly improve the care of COPD patients.
... In last fi ve years, due to the advent of genome-wide association studies (135)(136)(137), the genetics of COPD has moved beyond α-1 antitrypsin gene (138)(139)(140)(141)(142). Several genetic variants are reported to be associated with COPD in Indian population namely PIM3 allele of alpha-1-antitrypsin gene ( 143 ), GSTT1, GSTM1 and GSTM3 ( 144 , 145 ), PiZ and Pi S ( 146 ), cytokine gene polymorphisms (IL1B, IL1RN, TNF-α, and IL4) ( 144 ), CYP2E1 and NAT2 ( 147 ), GSTP1 and mEPHX ( 148 ), COX2 and p53 ( 149 ), CYP1A1, CYP1A2, and CYBA ( 150 ), TIMP-1 and α1AT ( 151 ). ...
The rising prevalence of the chronic obstructive pulmonary disease (COPD) is
generally attributed to smoking, since the role of other risk factors among nonsmokers
are not well established especially in low and middle income countries
like India. This is also reflected by the limited literature available on non-smoking
related COPD risk factors like indoor and outdoor air pollution. The present review
is an attempt to assess the influence of non-smoking risk factors on COPD and
its measures in Indian subcontinent. The most noteworthy factors among nonsmokers
appear to be the use of biomass fuel for cooking and heating purposes.
We observed that the studies undertaken to evaluate the role of such risk factors
are inconclusive due to weak methodologies and small sample sizes, may be due
to limited financial resources. The present review suggests the need of a nationally
representative study to estimate the effect of each of the potential modifiable risk
factor (other than smoking) for framing impactful public health policies to prevent
and manage COPD at community and population level in India.
... [28][29][30][31] Younger patients may differ from the majority of older patients with COPD in their disease pathology and natural history. 32 Hospital trusts were identified by their provider codes and were included in the analysis if they had a record of 100 COPD patient admissions during the study period. This criterion was applied to allow a comparison of hospitals that held responsibility for emergency admissions whose medical care might have been expected to include COPD. ...
Background
Hospitalizations for COPD are associated with poor patient prognosis. Length of stay (LOS) of COPD admissions in a large urban area and patient and hospital factors associated with it are described.
Methods
Retrospective longitudinal study. All COPD patients registered with London general practitioners and admitted as an emergency with COPD (2006–2010), not having been admitted with COPD in the preceding 12 months were included. Association of patient and hospital characteristics with mean LOS of COPD admissions was assessed. Association between hospital and LOS was determined by negative binomial regression.
Results
The total number of admissions was 38,504, from 22,462 patients. The mean LOS for first admissions fell by 0.8 days (95% confidence interval [CI]: 0.7–1.5) from 8.2 to 7.0 days between 2006 and 2010. Seventy-nine percent of first admissions were ≤10 days, with a mean LOS of 3.7 days (2009–2010). The mean LOS of successive COPD admissions of the same patients was the same or less throughout the study period. The interval between successive admissions fell from a mean of 357 days between the first and second admission to a mean of 19 days after eight admissions. Age accounted for 2.3% of the variance in LOS. Socioeconomic deprivation did not predict LOS. Fewer discharges happened at the weekend (1,893/day) than on weekdays (5,218/day). The mean LOS varied between hospitals, from 4.9 days (95% CI: 3.8–5.9) to 9.5 days (95% CI: 8.6–10.3) when adjusting for clustering, age, sex, and socioeconomic deprivation.
Conclusion
The fall in LOS of the first COPD admission between 2006 and 2010 reflects international trends. The stability of LOS in successive admissions suggests that increasing severity of disease does not affect recovery time from an exacerbation. Variations between hospitals of nearly 5 days in LOS for COPD admissions suggests that significant improvements in patient outcomes and in savings in health care utilization could be made in hospitals with longer LOS.
... As in usual COPD some episodes of exacerbation do not require intervention with new or increased medication [31]. However, episodes last longer in AATD than in usual COPD, and the severity of emphysema influences the symptoms and the duration [32]. The impact of exacerbations has received little attention in AATD, although the number is reflected in both spirometric and overall gas transfer decline [24], suggesting obstructive damage at least to the small airways. ...
The recognition of α-1-antitrypsin deficiency, its function, and its role in predisposition to the development of severe emphysema was a watershed in our understanding of the pathophysiology of the condition. This led to the concept and development of intravenous replacement therapy used worldwide to protect against lung damage induced by neutrophil elastase. Nevertheless, much remained unknown about the deficiency and its impact, although in recent years the genetic and clinical variations in manifestation have provided new insights into assessing impact, efficacy of therapy, and development of new therapeutic strategies, including gene therapy, and outcome measures, such as biomarkers and computed tomography. The current article reviews this progress over the preceding 50 years.
... Insbesondere traten keine Paravasate oder allergische Reaktionen auf. In der Literatur werden durchschnittlich bis zu 10 % "adverse events" unter der laufenden Therapie dokumentiert [1,8,19]. Bei den beobachteten 7 Patienten traten keine klinisch relevanten Ereignisse i. S. von Komplikationen auf. ...
Prognostic parameters and indicators of deterioration of prolastin substituted alpha 1 antitrypsin deficient COPD (AAT) are poorly defined. In particular, there is a lack of information how patients with AAT report exacerbations or how intravenous therapy with prolastin is tolerated and leads to a stabilization of the clinical course of the disease. In a prospective study seven patients were followed over 36 months who received i. v. prolastin at home. Both clinical parameters such as exacerbations and spirometric lung function tests were used to monitor the clinical course of the disease. During the time period given 2.1 exacerbations/year were documented, the average lung function loss over the period of 36 month was mean FEV1 1.02 ± 0.61 l/s to 0.94 ± 0.63 l/s and mean vital capacity 2.95 ± 0.82 l to 2.87 ± 0.81 l. Complications related to home based infusion therapy did not occur. No non elective hospitalisations were reported. Taken together, this prospective feasibility trial could show that home based i. v. therapy in patients with AAT is safe and leads to less exacerbations and loss of lung function as compared to the historical cohort.
© Georg Thieme Verlag KG Stuttgart · New York.
... In a recent study with diary cards, exacerbation treatment delay was associated with duration of exacerbation. Patients with worse lung function had shorter treatment delays (14). ...
Although less well appreciated than pulmonary emphysema, inflammation of the airways is an early and important finding in alpha-1 antitrypsin deficiency (AATD). The spectrum of clinical presentations of airways disease includes cough and wheezing that is frequently diagnosed as asthma. Study of the airways inflammation in sputum or the proximal airways usually reveals neutrophilic inflammation. Although there is significant phenotypic variation, tubular airways dilation consistent with bronchiectasis is a common finding in areas of panlobular emphysema in severely deficient AATD. Other phenotypes of varicose and saccular bronchiectasis have been described. Since AAT may impact the course of bacterial, mycobacterial and viral clearance, future studies of the airway microbiota will inform whether airway pathogens are responsible for some pulmonary AATD phenotypes. Whether airways disease improves with AAT augmentation therapy remains unknown.
