What factors influence the choice of treatment options for autoimmune PAP?
Click to see answer
The severity of the disease.
Click to see question
What factors influence the choice of treatment options for autoimmune PAP?
The severity of the disease.
What is the rate of spontaneous remission among patients with mild autoimmune PAP?
High rate of spontaneous remission.
How is the patient positioned during the WLL procedure?
In the lateral recumbent position with the lung to be lavaged nondependent.
What was observed in nonresponders receiving subcutaneous GM-CSF?
GM-CSF antibody titers did not decline.
What occurs to serum GM-CSF antibody titers in patients receiving nebulized GM-CSF?
Serum GM-CSF antibody titers increase despite clinical improvement.
What should be the maximum volume of unrecovered fluid in the lungs during WLL?
Not more than 200 to 300 mL.
What are the most common symptoms of PAP?
Dyspnea and cough.
How do initial BAL fluid levels of GM-CSF antibodies correlate with PAP severity?
They correlate better with the severity of PAP than serum titers.
When is recombinant GM-CSF therapy reserved for patients?
For patients who cannot undergo or have failed WLL.
What are the underlying causes of secondary PAP?
Certain hematologic/immunologic/metabolic diseases, inhalational exposures, and infections.
What characterizes moderate-to-severe symptoms in PAP patients?
Dyspnea with minimal exertion or at rest and requiring supplemental oxygen.
What causes primary PAP?
Disorders of GM-CSF signaling due to GM-CSF antibodies.
What monitoring is necessary during the WLL procedure?
Oxygenation, dynamic lung compliance, endotracheal tube position, and recovery of infused saline.
Why should patients with PAP be advised not to smoke cigarettes?
Smoking requires twice as many sessions of whole lung lavage compared to nonsmokers.
What improvement was observed in the largest randomized trial of GM-CSF therapy?
Significant improvement in AaO gradient and DLCO compared to placebo.
What is assessed to determine the appropriate treatment for PAP?
Severity of PAP using symptoms, serum LDH levels, GM-CSF antibody titers, pulmonary function tests, and HRCT imaging.
How many forms of PAP are recognized?
Five forms.
What are the proportions of stable, improved, and worsening disease among symptomatic patients?
About 45% stable, 30% improved, and 25% worsening.
What is the primary therapy used for autoimmune PAP?
Whole Lung Lavage (WLL).
What is secondary PAP?
PAP that occurs due to underlying disorders affecting alveolar macrophage function, such as certain hematologic, immunologic, or metabolic diseases.
What is obtained after the WLL procedure to check for complications?
An upright chest radiograph.
What is pulmonary alveolar proteinosis (PAP)?
A diffuse lung disease characterized by the accumulation of amorphous, PAS-positive lipoproteinaceous material in the distal air spaces.
What pulmonary function tests are used in assessing PAP severity?
Lung volumes, diffusing capacity, and six-minute walk with oxygen saturation determination.
What is the volume of normal saline typically used for lavage?
15 to 20 liters.
What is the management approach for asymptomatic or mild disease in patients with PAP?
They do not require immediate treatment and can be observed with periodic reassessment of symptoms, oxygen saturation, pulmonary function tests, and/or chest imaging.
What percentage of patients with autoimmune PAP managed without therapeutic intervention remained stable or achieved remission?
39 out of 40 patients.
What are some complications associated with WLL?
Malpositioning of the endotracheal tube, saline spillover, intraprocedural hypoxemia, pneumothorax, and hydropneumothorax.
What was the improvement in DLCO for the continuous GM-CSF group compared to placebo?
12.0 percent versus 4.2 percent.
What investigational therapies are considered for refractory disease?
Rituximab, therapeutic plasma exchange, participation in clinical trials, or lung transplantation.
What improvements were observed after rituximab treatment in the study?
Significant improvements in arterial oxygen tension (PaO2) and A-aO2 difference at three and six months.
What was the improvement in SGRQ score for the continuous molgramostim group compared to placebo?
-7.4 points.
What is therapeutic plasma exchange (TPE) used for in patients with autoimmune PAP?
It is used for patients who have failed to improve with whole lung lavage (WLL).
What therapies have been employed for refractory autoimmune PAP?
Rituximab and therapeutic plasma exchange.
How are patients with lysinuric protein intolerance managed?
With dietary modification, occasionally WLL, and rarely inhaled GM-CSF in refractory cases.
What condition is associated with anti-GM-CSF antibodies in pediatric patients?
Pulmonary alveolar proteinosis.
What type of endotracheal tube is used during WLL?
A double-lumen endotracheal tube.
What procedure is performed on the worse side of the lung during WLL?
Lavage.
What temperature should the normal saline be warmed to before instillation?
37ºC.
What technique is suggested to enhance the efficacy of WLL?
Repetitive manual hyperinflation and intermittent chest percussions.
What is the optimal treatment for secondary, hereditary, and congenital PAP?
The optimal treatment has not been determined.
How is the whole lung lavage typically performed?
One lung is lavaged in the first procedure, followed by the opposite lung one to two weeks later.
What does the development of HRCT findings consistent with parenchymal fibrosis indicate?
It portends a poorer outcome.
What improvements were noted in the modified Medical Research Council dyspnea scale and DLCO?
Borderline improvements.
What was the mean change in alveolar-arterial oxygen gradient for the GM-CSF group compared to placebo?
−4.50±9.03 mm Hg versus 0.17±10.50 mm Hg.
What does radiographic imaging typically reveal in PAP patients?
Bilateral symmetric alveolar opacities located centrally in mid and lower lung zones, often in a 'bat wing' distribution.
What should be monitored during the treatment or observation of PAP?
Symptoms, spirometry, diffusing capacity, ambulatory oximetry, and chest CT scan.
How is recombinant GM-CSF administered for inhalational therapy?
Reconstituted in 2 mL of normal saline and administered via nebulizer.
What percentage of patients achieved sustained remission after one lavage in a study of 80 patients?
70 percent.
How long after the first lung lavage is the opposite lung typically lavaged?
One to two weeks later.
How did the rate of WLL change over time in the continuous therapy group?
It decreased over time.
What is the most important intervention for secondary PAP due to inhalational exposures?
Completely discontinue further exposures.
What hypothesis has been proposed regarding some cases of autoimmune PAP?
They may result from an acquired clonal disorder of hematopoietic cells.
What is the treatment approach for secondary and hereditary PAP?
Treatment options depend on the specific cause and may include whole lung lavage for moderate-to-severe symptoms.
What did the study by Kariman et al. in 1984 investigate?
Prospective clinical experience in 23 patients with pulmonary alveolar proteinosis over 15 years.
What did the open-label trial of rituximab therapy in pulmonary alveolar proteinosis demonstrate?
It provided evidence for the efficacy of rituximab in treating the condition.
How does rituximab therapy affect alveolar macrophage lipid homeostasis?
It improves lipid homeostasis in alveolar macrophages.
What treatment options were discussed alongside plasmapheresis for alveolar proteinosis?
GM-CSF and other therapies.
What was the outcome of statin therapy in a case report for pulmonary alveolar proteinosis?
Successful treatment without hypercholesterolemia.
What was the outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis?
Retrospective cohort study results.
What did the review by Vymazal and Krecmerova focus on?
Respiratory strategies and airway management in patients with pulmonary alveolar proteinosis.
What type of dust inhalation was associated with alveolar proteinosis in a 2016 study?
Aluminium dust.
What did Seymour et al. (1998) find regarding the hematopoietic response to GM-CSF?
They observed an attenuated response in patients with acquired pulmonary alveolar proteinosis.
What is the typical anesthesia used for Whole Lung Lavage (WLL)?
General anesthesia.
What is the purpose of recombinant GM-CSF in the context of PAP?
To improve gas exchange and support patients during procedures like WLL.
What is congenital PAP?
Disorders of surfactant production or metabolism due to genetic variants in surfactant and other proteins.
What happens to GM-CSF antibody titers in responders to subcutaneous GM-CSF treatment?
Serial GM-CSF antibody titers decline.
What is the advantage of nebulized GM-CSF over subcutaneous administration?
Greater ease of administration and possibly better response.
What treatment options are available for patients with moderate-to-severe respiratory impairment?
Whole lung lavage (WLL) or a trial of experimental treatment such as subcutaneous or inhaled GM-CSF, or rituximab.
What adverse effects are associated with GM-CSF therapy?
Mild effects including fever, fatigue, headache, and injection site complications.
What potential treatment may reverse PAP due to GM-CSF receptor variants?
Hematopoietic stem cell transplantation (HSCT).
What is lung transplantation reserved for in the context of PAP?
Selected patients with severe, refractory PAP.
What did the study by Inoue et al. in 2008 characterize?
A large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan.
What infectious complications are associated with PAP?
Increased risk of superinfection with opportunistic organisms such as Nocardia, mycobacteria, and various fungi.
What specific therapies may respond in certain types of secondary PAP?
Treatment of underlying hematologic malignancy, hematopoietic stem cell transplantation, and avoidance of occupational dust exposures.
What comparison was made in the study by Hammon et al. regarding pulmonary alveolar proteinosis?
Comparison of manual to mechanical chest percussion for clearance of alveolar material.
What was the finding of Grutters et al. regarding whole lung lavage treatment?
Increased efficacy using a new modified lavage technique.
What role do GM-CSF autoantibodies play in pulmonary alveolar proteinosis?
They are associated with neutrophil dysfunction.
What was the focus of the study by Tian et al. (2020)?
The effectiveness of inhaled GM-CSF for mild-to-moderate autoimmune pulmonary alveolar proteinosis over six months.
What percentage of asymptomatic patients with autoimmune PAP showed worsening during follow-up?
8 percent.
What is used to support patients with severely compromised gas exchange during WLL?
Extracorporeal membrane oxygenation.
What characterizes asymptomatic or mild symptoms in PAP patients?
Little or no physiologic impairment, normal to mildly reduced DLCO, and normal SpO2 at rest.
What are some indications for considering whole lung lavage?
Resting PaO2 <65 mmHg, A-aO2 difference ≥ 40 mmHg at rest, severe dyspnea and hypoxemia at rest or on exercise.
What are some contraindications for whole lung lavage?
Uncorrectable clotting disorders, anesthetic risks, and cardiopulmonary instability.
What is the optimal therapy for patients with refractory disease despite WLL and GM-CSF therapy?
The optimal therapy is not known and must be decided on a case-by-case basis.
What was the dosage of rituximab in the phase II study for autoimmune PAP?
1 g infused intravenously for two doses about two weeks apart.
What should cigarette smokers with PAP be advised to do?
Stop smoking.
What percentage of PAP patients may achieve remission or remain stable without specific therapy?
Up to 30 percent.
What was the outcome of one patient who underwent therapeutic plasma exchange?
One patient did not improve, while another responded to low intensity TPE over two months.
What were the results of WLL for patients with PAP following inhalational exposure?
Results have been mixed; some patients responded while others did not.
What does HSCT aim to prevent in patients with PAP?
The return of alveolar macrophages with aberrant GM-CSF receptors.
What has been noted about lung transplantation in patients with autoimmune PAP?
Some patients developed recurrent disease in the lung allograft.
What is the therapeutic effectiveness of rituximab in autoimmune pulmonary alveolar proteinosis?
Rituximab has shown effectiveness in patients unresponsive to other treatments.
What syndrome is discussed in the Clin Chest Med 2016 article by Suzuki and Trapnell?
Pulmonary Alveolar Proteinosis Syndrome.
What therapy was tested in the 2010 Am J Respir Crit Care Med publication for pulmonary alveolar proteinosis?
Inhaled granulocyte/macrophage-colony stimulating factor.
What was reported in the 2001 Thorax publication regarding GM-CSF therapy?
A complete response to GM-CSF therapy in pulmonary alveolar proteinosis.
What did the 2024 Eur Respir J study find about inhaled recombinant GM-CSF?
It reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients.
What procedure was discussed in the 2009 Chest article by Michaud et al.?
Whole-lung lavage for pulmonary alveolar proteinosis.
What is the role of aerosol granulocyte-macrophage colony-stimulating factor (GM-CSF) in pulmonary alveolar proteinosis?
It is used to improve lung clearance in patients with the condition.
What was the outcome of the study on inhaled Molgramostim therapy in autoimmune pulmonary alveolar proteinosis?
It showed effectiveness in treating the condition.
What vaccinations should patients with PAP obtain annually?
Influenza, COVID-19, pneumococcal pneumonia, and respiratory syncytial virus.
What was the outcome of sequential treatment with inhaled GM-CSF after WLL?
It greatly reduced the need for repeat WLL over 30 months of follow-up.
What does the initial lavage effluent typically appear like?
Thick and milky.
Which group of patients is more likely to require repeat WLL?
Cigarette smokers.
What is the minimal clinically important difference for the SGRQ score?
-4 points.
What has been the success rate of WLL for patients with myelodysplastic syndrome?
Mixed success.
What was the difference in A-aO2 between the GM-CSF treatment group and placebo after 25 weeks?
-5.70.
Are glucocorticoids indicated for autoimmune PAP?
No, glucocorticoids are not indicated for autoimmune PAP.
How might statins be beneficial for patients with autoimmune PAP?
They may improve surfactant uptake and clearance by alveolar macrophages.
What was observed in a patient with a CSF2RB mutation after lung transplantation?
Developed recurrent PAP after nine months.
What does the study by Sui et al. in 2017 assess?
Quantitative assessment of pulmonary alveolar proteinosis with ultra-dose CT and correlation with pulmonary function tests.
What is the clinical significance of anti-GM-CSF antibodies in idiopathic pulmonary alveolar proteinosis according to Lin et al.?
It was discussed in their 2006 study published in Thorax.
What treatment method was evaluated in the 2015 Chin Med J study for autoimmune pulmonary alveolar proteinosis?
Whole Lung Lavage.
What was the focus of the 2017 Ann Am Thorac Soc report by Ohkouchi et al.?
Sequential Granulocyte-Macrophage Colony-Stimulating Factor Inhalation after Whole-Lung Lavage.
What did the 1965 Ann Intern Med report by Larson and Gordinier discuss?
Six cases of pulmonary alveolar proteinosis and a new theory.
What insights were gained from the single-center cohort of 70 patients in the 2011 Respir Med article by Bonella et al.?
New insights into pulmonary alveolar proteinosis.
What progress is discussed in the study by Seymour and Presneill regarding pulmonary alveolar proteinosis?
Progress in the first 44 years of understanding and treatment.
What was the finding of Ohashi et al. (2012) regarding GM-CSF inhalation?
It provides direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis.
What did Ohashi et al. (2012) report about GM-CSF autoantibodies?
They found reduced GM-CSF autoantibodies in improved lung conditions of autoimmune pulmonary alveolar proteinosis patients.
What is the most widely accepted and effective treatment for patients with moderate-to-severe symptoms and hypoxemia?
Whole lung lavage (WLL) under general anesthesia.
How often do some patients require repeat lung lavages after WLL?
At intervals of 6 to 12 months.
What initial DLCO percentage is associated with a higher likelihood of requiring additional WLL?
42 percent predicted or less.
What vaccinations are advised for all patients with PAP?
Annual vaccinations against influenza and COVID-19, and age-appropriate vaccinations against pneumococcal pneumonia and respiratory syncytial virus.
What were the initial and subsequent dosages of subcutaneous GM-CSF in the trial?
Starting at 250 mcg/day for one month, increasing to 5 mcg/kg/day for the second month, and 9 mcg/kg/day for the third month.
What adverse event was more frequent in the continuous treatment group?
Chest pain.
What may recombinant GM-CSF help reduce in patients with autoimmune PAP?
The need for or frequency of recurrent whole lung lavage.
Why do patients with PAP have an increased risk of infections?
Due to impaired macrophage and neutrophil function.
What vaccinations should all patients with PAP be counseled to obtain annually?
Influenza, COVID-19, respiratory syncytial virus, and pneumococcal pneumonia (if no contraindications).
What has been observed in patients with autoimmune PAP treated with statins?
Improvements in lung function, oxygenation, and radiologic findings.
What was the duration of experience reported in the study by Kaenmuang and Navasakulpong regarding whole lung lavage?
20 years.
What aspect of whole lung lavage is discussed in the study by Tan et al.?
Anesthetic management for whole lung lavage in patients with pulmonary alveolar proteinosis.
What did Bonella et al. study in their 2012 research?
Wash-out kinetics and efficacy of a modified lavage technique for alveolar proteinosis.
What condition is described in the study by Nimmatoori et al.?
Pulmonary alveolar proteinosis characterized by milky fluid from the lungs.
What occupational exposure was linked to pulmonary alveolar proteinosis in a 2010 study?
Indium processing facility.
What organism was isolated in patients with pulmonary alveolar proteinosis according to Witty et al.?
Mycobacteria.
What was the treatment difference in AaO gradient between continuous GM-CSF and placebo after 24 weeks?
-6.2 mmHg.
What is the role of rituximab in the treatment of PAP?
It may be tried if there is inadequate response to whole lung lavage and GM-CSF or if they are associated with unacceptable side effects.
What procedure is often used for patients with moderate to severe symptoms of PAP?
Whole lung lavage (WLL).
What was the response rate to subcutaneous recombinant GM-CSF?
Slightly less than 50 percent.
What treatment may improve secondary PAP due to hematologic dyscrasias?
Treatment of the underlying hematologic malignancy or myelodysplasia.
What correlation was observed with declining serum GM-CSF antibody levels?
They appear to correlate with a positive response to GM-CSF therapy.
What is a potential future direction for treating hereditary PAP?
Derivation of macrophages from gene-corrected pluripotent stem cells.
What is recommended for patients with minimal or mild disease of PAP?
Supportive care with supplemental oxygen, as needed.
What congenital disorders are associated with PAP?
Variants in genes for surfactant proteins (SP)-B or C, and others involved in surfactant metabolism.
What does the research by Bonfield et al. in 2002 suggest about anti-GM-CSF titer?
It predicts response to GM-CSF therapy in pulmonary alveolar proteinosis.
What is the focus of the open-label trial mentioned in the 2006 Chest publication?
Granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis.
What did Leth et al. review in their 2013 study regarding autoimmune pulmonary alveolar proteinosis?
Treatment options.
What did Claypool et al. update in their 1984 Chest article?
Clinical diagnosis, management, and pathogenesis of pulmonary alveolar proteinosis.
What long-term benefit was reported by Beccaria et al. in their 2004 study?
Durable benefit after whole lung lavage in pulmonary alveolar proteinosis.
What can secondary alveolar proteinosis cause in leukemic patients?
Reversible respiratory failure.
What mutation was identified in the patient who experienced recurrence of pulmonary alveolar proteinosis after bilateral lung transplantation?
A nonsense mutation in CSF2RB.
What is the significance of nocardia in relation to pulmonary alveolar proteinosis?
It can induce granulocyte macrophage colony-stimulating factor, which is neutralized by autoantibodies.
What is the suggested treatment approach for patients with moderate to severe symptoms?
A stepwise approach beginning with whole lung lavage, followed by inhaled GM-CSF if necessary.
What type of anesthesia is used for the whole lung lavage procedure?
General anesthesia.
What percentage of PAP patients achieve remission or stability with one or more whole lung lavages (WLLs)?
70 to 90 percent.
What is the increased risk for patients with PAP?
Superinfection with opportunistic organisms such as Nocardia, actinomyces, mycobacteria, and various fungi.
What role do glucocorticoids play in the treatment of autoimmune PAP?
There is no role for glucocorticoids or other immunosuppressive agents as primary therapy.
What is the recommended treatment for patients with moderate-to-severe dyspnea and hypoxemia due to autoimmune PAP?
Whole lung lavage (WLL).
What treatment was studied in the 2019 N Engl J Med article by Tazawa et al. for Pulmonary Alveolar Proteinosis?
Inhaled GM-CSF.
What type of study was conducted on rituximab for autoimmune alveolar proteinosis?
A real-life cohort study.
What was the focus of the plasmapheresis protocol for pulmonary alveolar proteinosis?
It was designed for refractory cases.
What was reported in the case of living-donor lobar lung transplantation for pulmonary alveolar proteinosis?
Successful treatment in an adult patient.
What advancement was made in gene correction for pulmonary alveolar proteinosis?
Human induced pluripotent stem cells were corrected to repair the cellular phenotype.
What treatment is discussed by Kavuru et al. for pulmonary alveolar proteinosis?
Exogenous granulocyte-macrophage colony-stimulating factor administration.
What did the systematic review by Munsif et al. (2023) focus on?
The use of nebulized GM-CSF in autoimmune pulmonary alveolar proteinosis.
What is the significance of Rituximab therapy in autoimmune pulmonary alveolar proteinosis according to Borie et al. (2009)?
It is explored as a treatment option for the condition.
What percentage of patients with refractory autoimmune PAP showed objective improvement after treatment with Rituximab?
30 percent (4 out of 13 patients).
Is recombinant GM-CSF approved for use in autoimmune PAP?
No, it is not approved for autoimmune PAP.
What challenge do many patients with autoimmune PAP face regarding GM-CSF therapy?
They may not manifest a normal hematologic response and may require very high doses for a modest elevation in white blood cell count.
What effect did GM-CSF inhalation have on GM-CSF autoantibodies?
It was associated with a decrease in GM-CSF autoantibodies.
What is the focus of the study by Shah et al. in 2000?
Clinical aspects and current concepts on the pathogenesis of pulmonary alveolar proteinosis.
What novel pharmacotherapy was studied for pulmonary alveolar proteinosis in 2018?
Statin.
What defect is associated with human pulmonary alveolar proteinosis according to a 1997 study?
Defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression.
What is secondary pulmonary alveolar proteinosis associated with?
Hematologic malignancies.
What event led to the development of pulmonary alveolar proteinosis due to dust exposure?
The Great East Japan Earthquake.
What type of infections are patients with pulmonary alveolar proteinosis at risk for?
Opportunistic infections.
What are the clinical features and outcomes of pulmonary alveolar proteinosis as discussed by Goldstein et al.?
The study provides insights into the clinical features and outcomes of the disease.
What was the outcome regarding adverse events between GM-CSF and placebo-treated patients?
No significant difference.
What is the significance of clinical trials for patients with PAP?
Patients may wish to participate in trials for treatments like rituximab and GM-CSF.
What was the focus of the research by Kumar et al. in 2018?
Pathophysiology and clinical approach to pulmonary alveolar proteinosis in adults.
What treatment option is discussed by Luisetti et al. in 2009 for pulmonary alveolar proteinosis?
Plasmapheresis.
What is the focus of the study by Gay et al. published in Respiration in 2017?
Efficacy of Whole-Lung Lavage in Pulmonary Alveolar Proteinosis.
What type of survey did Campo et al. conduct in their 2016 study?
A global survey of current practices and procedures for whole lung lavage therapy.
What complication was noted following double lung transplantation?
Recurrent alveolar proteinosis.
What innovative approach was used for modeling hereditary pulmonary alveolar proteinosis?
Murine iPSC-derived macrophages.
What did the study by Robinson et al. (2009) analyze?
The longitudinal response to aerosolized GM-CSF in adolescents with autoimmune pulmonary alveolar proteinosis.
What was the focus of the study by Mabo et al. regarding pulmonary alveolar proteinosis?
Infections in autoimmune pulmonary alveolar proteinosis.
What was the outcome of GM-CSF therapy in acquired alveolar proteinosis according to the 1996 N Engl J Med study?
Efficacy of granulocyte-macrophage colony-stimulating factor.
What did the 2003 Thorax study investigate in relation to GM-CSF therapy?
The relationship of anti-GM-CSF antibody concentration, surfactant protein levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy.
What was the focus of the meta-analysis conducted by Khan et al. in 2012?
Effectiveness of granulocyte-macrophage colony-stimulating factor therapy in autoimmune pulmonary alveolar proteinosis.
How does secondary pulmonary alveolar proteinosis complicate myelodysplastic syndrome?
It results in worsening of prognosis.
What are the two transplant options discussed for pulmonary alveolar proteinosis?
Lung transplant or bone marrow transplant.
What imaging technique was used to assess pulmonary fibrosis in patients with pulmonary alveolar proteinosis?
High-Resolution CT.
