Survey Provides Updated Expert Opinions on Severe AATD Assessment, Monitoring

Marc Miravitlles, MD, PhD

Credit: Vall d’Hebron

Findings from a recent study are helping to address a current lack of consistent guidance on the diagnosis, treatment, and management of patients with severe alpha-1 antitrypsin deficiency (AATD) by providing updated expert opinions for patients with stable and worsening disease.¹

Leveraging survey responses from members of the European Alpha-1 Research Collaboration (EARCO), the study compiles opinions from pulmonologists from across 15 countries in Europe regarding the assessment and management of severe AATD, potentially informing a standardized treatment pathway and helping to improve patient outcomes.¹

“Discordance currently exists among published guidelines for the assessment and management of patients with severe AATD,” Marc Miravitlles, MD, PhD, ​​a pulmonologist and senior researcher at the Vall d’Hebron University Hospital and the Vall d’Hebron Research Institute in Spain, and colleagues wrote.¹ “To our knowledge, this is the first study that attempts to establish a consensus for the treatment and monitoring of patients with AATD using Delphi consensus methodology.”

To establish a consensus for the assessment and management of patients with severe AATD, investigators utilized the experience of EARCO members through a Delphi study to determine the optimal assessment, monitoring, and management of patients with severe AATD. EARCO is a pan-European network committed to promoting clinical research and education in AATD. It is an initiative of the European Respiratory Society and was established to promote research, clinical care, and awareness of AATD in Europe.^1,2

Members of EARCO were invited to participate based on their expertise and experience in treating patients with AATD. The Delphi survey was conducted online, and respondents were asked to consider the initial assessment and routine follow-up/management of adults diagnosed with AATD and lung disease for those with no respiratory symptoms and stable lung function with normal age-related deterioration in spirometry over time; those with stable respiratory disease; and those with worsening respiratory disease.¹

Investigators asked respondents to indicate their agreement with the proposed statements using a Likert scale of 1–7. Levels of agreement between respondents were calculated using a weighted average, and the following thresholds were applied: consensus in negative (≤ 2); agreement in negative (≤ 3); no consensus or agreement (3.1–4.9); agreement (≥ 5); consensus (≥ 6).¹

Two rounds of a Delphi survey were completed online by members of EARCO. Round 1 was sent to 103 members of EARCO via email in February 2022 and consisted of 109 questions. In total, 38 (36.9%) pulmonologists from across 15 countries completed all 109 questions. For questions where no positive consensus was reached in Round 1, questions were asked again in Round 2 with the omission of answer choices that reached consensus in negative in Round 1. Round 2 of the survey consisted of 79 questions and was sent to all individuals who fully completed Round 1 in November 2022, and 36 (94.7%) completed all of the questions.¹

Patients with No Respiratory Symptoms

For spirometry, consensus was reached for the frequency of assessment as well as the recording of FEV1, forced vital capacity (FVC), and FEV1/FVC, while the recording of other parameters and the measurement of spirometry pre-/post-bronchodilator (BD) reached agreement. Consensus was also reached for the use of body plethysmography to record total lung capacity (TLC), residual volume (RV), and RV/TLC, while the recording of airway resistance (Raw), specific airway resistance (sRaw), functional residual capacity (FRC), FRC/TLC, and the frequency of body plethysmography assessment, reached agreement.¹

Consensus was reached on the frequency of diffusion capacity and there was agreement for the utilization of HRCT. However, there was no consensus or agreement on the frequency of LDCT and 6MWD, and investigators noted responses were highly variable for these categories in comparison to others.¹

Patients with Stable Respiratory Disease

Consensus was achieved for the spirometric recording of FEV1, FVC, and FEV1/FVC. The recording of other spirometry parameters reached agreement, as did the spirometry assessment frequency and the measurement of spirometry in relation to BD. For body plethysmography, there was consensus for the recording of TLC, RV, and RV/TLC, and agreement for the recording of other parameters, as well as body plethysmography assessment frequency. However, as for patients with no respiratory disease, the assessment of body plethysmography pre-/post-BD did not reach consensus or agreement.¹

Consensus was also achieved for the annual assessment of diffusion capacity and for the use of HRCT in patients with stable respiratory disease. Again, responses were highly variable for questions regarding LDCT and the 6MWD assessment.¹

Regarding the initiation of augmentation therapy, consensus was reached that before initiating such treatment, it is essential to confirm AATD-related lung disease and measure AAT levels. Agreement was reached on several conditions for starting therapy: patients should have abstained from smoking for > 6 months, therapy should only begin when AAT levels are < 11 µM, the patient's age should be considered, emphysema should be confirmed by CT, and FEV1 deterioration should guide the decision. Additionally, extended interval dosing was deemed an acceptable strategy, with AAT levels monitored at trough after any changes in dose or interval.¹

Patients with Worsening Respiratory Disease

Consensus was achieved for recording FEV1, FVC, and FEV1/FVC, TLC, RV, and RV/TLC. For spirometry, there was also agreement on assessment frequency and whether assessment should be pre-/post-BD. For body plethysmography, there was no consensus or agreement for assessment frequency or assessment in relation to BD and no consensus or agreement for diffusion capacity.¹

For HRCT, consensus was achieved for utilization in patients with worsening respiratory disease. For patients with no respiratory symptoms and those with stable disease, responses were highly variable for questions regarding LDCT and the 6MWD assessment compared to other categories for patients with worsening respiratory disease.¹

Regarding the initiation of augmentation therapy in patients with worsening respiratory disease, only 1 statement reached consensus; AAT levels should be measured before commencement. Respondents agreed on all other statements on the initiation of augmentation therapy but did not reach consensus.¹

Investigators acknowledged multiple limitations to these findings, including the inclusion of only 2 survey rounds due to the small size of the study; the low participation rate among EARCO members; the unequal geographical spread of the participants, with approximately a quarter of all respondents being from Spain; the fact that most participants were from countries with AAT reimbursement policies; and recognition that physicians may be influenced by their knowledge of the specific guidelines that they use.¹

“The present study provides updated expert opinions for the assessment and monitoring of patients with severe AATD, for those with stable and worsening disease, which were developed from the views of European respiratory physicians,” investigators concluded.¹ “Continuing to build the evidence base for the management of AATD is essential to support access to treatment and ensuring optimal access to effective care in AATD is something that EARCO is deeply committed to.”

References

1. ^{Miravitlles M, Turner AM, Sucena M, et al. Assessment and monitoring of lung disease in patients with severe alpha 1 antitrypsin deficiency: a european delphi consensus of the EARCO group. Respir Res. https://doi.org/10.1186/s12931-024-02929-5}
2. ^{Miravitlles M, Chorostowska-Wynimko J, Ferrarotti I, et al. The European Alpha-1 Research Collaboration (EARCO): a new ERS Clinical Research Collaboration to promote research in alpha-1 antitrypsin deficiency. European Respiratory Journal. doi:10.1183/13993003.00138-2019}