alveolar proteinosis

1. Contact: dr.abedini110@gmail.com
https://sa.sbmu.ac.ir
An Eleven-Year
Retrospective Cross
Sectional Study on
Pulmonary Alveolar
Proteinosis
Dr. Atefeh Abedini, MD
Interventional
Pulmonologist
NRITLD, Shahid
Beheshti University of
Medical Sciences

2. No Disclouser
dr.abedini110@gmail.com

3. Sarcoidosis group
National Research Institute of
Tuberculosis and Lung Diseases
(NRITLD) @ Shahid Beheshti
University of Medical Sciences,
Tehran/Iran
Dr. Atefeh Abedini

4. – The Sarcoidosis clinic at Masih Daneshvari
Hospital is recognized as the referral for
Sarcoidosis research in Iran which is a
designated center for expertise in the treatment
of Sarcoidosis is related to WASOG.
– The Sarcoidosis research center of NRITLD is
led by Dr. Atefeh Abedini who is a nationally
recognized physician for her expertise in
Sarcoidosis.

5. Pulmonary alveolar
proteinosis (PAP)
‒ PAP is a rare disease characterized by alveolar
accumulation of surfactant composed of proteins
and lipids due to defective surfactant clearance
by alveolar macrophages.
‒ Diagnosis of PAP is initiated by computed
tomography (CT) scan and confirmed by staining
of bronchoalveolar lavage fluid (BALF)

6. Pulmonary alveolar
proteinosis (PAP)
Whole-lung lavage (WLL) which is known as the gold
standard treatment for PAP was used for the first time
among Iranian PAP patients in current study.
Nevertheless, reports on characteristics of this disease in
Middle East are limited.
WLL had never used as the treatment in Iranian PAP
patients before current study.
In this research, it was decided to describe demographic,
epidemiologic, clinical features and treatment outcomes of
Iranian PAP patients during eleven years.

7. Materials and Methods

8. Study design
– This study was conducted as a retrospective cross sectional
study at Iran referral respiratory hospital.
– Forty five PAP patients (21 females and 24 males) consist of
42 cases as the “adult group” and three cases under 14 years
old as the “pediatric group” were included in this study based
on definitive diagnosis of PAP through Broncho Alveolar
Lavage (BAL) or Trans-Bronchial Lung Biopsy (TBLB) between
March 2004 and March 2015.
– Mean age ± SD at diagnosis time was 30.33±14.56 years old.
– This study was approved by the ethics committee of the
hospital. Moreover, written consent was obtained from all
patients before participation in the study.

9. Diagnostic and treatment
methods
– The diagnosis of PAP was based on these three
criteria which was different in each case including
CLINICAL history, radiographic findings on HRCT in
some cases, pathological/cytological findings.
– Definitive diagnosis of PAP was confirmed by
Bronchoalveolar lavage or lung biopsy (trans-
bronchial or open).

10. Diagnostic and treatment
methods
– Some patients that BAL smears or cultures were
positive for Mycobactrium TB had been treated for TB
about six months with Isoniazid and Rifampicin AND
etambotol and pyrazinamide Before conducting the
first WLL.
– We made sure that all patients had been treated
completely, not only regarding TB but also regarding
other infections.
– WLL which is often chosen as the first option of PAP
disease treatment was performed for the first time in
Iranian population.

11. Whole Lung Lavage
– This procedure was performed by an experienced
lavage team including interventional pulmonologist,
anesthesiologist, nurse and respiratory therapist. WLL
was performed under general anesthesia.
– The lungs ventilated with FiO2 of 1.0 for 15 minutes.
Then degassing was performed by rate of up to 125
mL/min for 10 -15 minutes. Warm saline (to 37 ℃)
flowed into the lung slowly.
– This filling continued up to the estimated functional
residual capacity volume of that lung and then suctions
performed.
– Repeated cycles of lung filling with warmed saline
(500–1000 cc) continued for 2 minutes with chest
percussion therapy.

12. Whole Lung Lavage
– Lavages had been continued under monitoring until
the returned fluid was clear.
– Lavage is the main treatment of PAP. In our study all
patients received whole lung lavage as the treatment
but We do not perform lavages of both lungs at the
same time.
– Number of lavages were different from one to 12
based on patient's O2 saturation, medical states and
CT findings of each patient.

13. Bronchoalveolar lavage
– BAL was performed by the standard protocol
confirmed by the department of Pulmonary Medicine.
– Through a two-way syringe, 20 ml of sterile saline
(0.9%) was inserted in the suction port, after that the
fluid was pulled back immediately by use of 50-100
mmHg negative pressure suction.
– The lavage and suction process repeated up to four
times. The collected fluid was clinically analyzed. The
details of this procedure were recorded.

14. Trans-Bronchial Lung Biopsy
– Trans-Bronchial Lung Biopsy (TBLB) was performed by
experienced pulmonologist under conscious sedation.
– Six-eight tissue specimens were obtained from the middle
lobe right and lower lobe of all cases through standard
biopsy forceps (sample size ~ 3mm).

15. Data Collection
– Demographic and historical data, signs and
symptoms, radiologic features, diagnostic modalities
and number of conducted WLL were recorded.
– Efficiency of WLL was assessed by comparing
Spirometric parameters, arterial blood gas analysis
(PaO₂, PaCO₂ and O₂ saturation) and Six Minute
Walk Test (6MWT) results before and after WLL

16. Results

19. Discussion

20. - WLL was found as the sufficient treatment for
PAP patients due to significant improvement of
spirometric parameters, oxygen saturation,
arterial blood gas analysis and 6MWD after
WLL (P value <0.0001).
- This confirmed previous statements that
ascribed WLL as the sufficient treatment.
- The sufficiency of BAL and TBLB as
diagnostic methods were consistent with
results of Inoue et al, Xu et al and Bonella et al
studies but different from Seymur meta-
analysis.

21. - Mean age at diagnosis among adult PAP
patients was lower in Iranian population in
comparison to Japanese, German, Chinese and
Korean population but it was comparable to
Israeli population.
- This could raise the possibility that geographic
or ethnic factors play a role in determining the
manifestation age of PAP. This possibility
requires further investigation.
- Regarding gender distribution, there was no
predominance in males and male to female ratio
was 1.1, similar to studies conducted in
Germany and Israel and in contrast to most
previous studies which reported 2-fold
predominance in males.

22. - Nine patients (20%) had history of dust
exposure similar to report in Inoue study but
lower than report of Bonella et al.
- An overall number of 11 patients (24.4%) had
an underlying comorbidity (active tuberculosis)
or dust exposure.
- Those patients who had active tuberculosis or
dust exposure might have secondary PAP,
however we could not definitely distinguish
primary from secondary PAP due to lack of
access to laboratory facilities for measuring
anti-GM-CSF autoantibody.
- This is one of the limitations of the present
study.

23. - Four variables of hemoptysis, concomitant
tuberculosis, 6MWD and oxygen saturation
after lavages were significantly different
between treatment failure and treatment
responder groups.
- Given the fact that our country is endemic for
tuberculosis-a disease which is a frequent cause
of hemoptysis and since hemoptysis is an
independent predictor for treatment failure in
our patients, considering concomitant
tuberculosis in PAP patients and proper
treatment of tuberculosis may improve outcome
in PAP patients.

24. Conclusion
– To conclude, regarding the significant
improvement in spirometry result, ABG gas
analysis and 6MWD after all lavages, our study
revealed sufficiency of WLL as the PAP patients'
treatment.
– Hemoptysis was the only independent factor
which can predict treatment failure therefore in
Iran as an endemic country for tuberculosis,
proper treatment of tuberculosis may improve
outcome in PAP patients.

25. Thank You for Your Attention