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\begin{document}

\title{Measures of Ventilation Heterogeneity Mapped with Hyperpolarized
Helium-3 (HHe-3) MRI Demonstrate a T2-High Phenotype in Asthma}



\author[1]{William Teague}%
\author[2]{Jaime Mata}%
\author[2]{Kun Qing}%
\author[2]{Nicholas Tustison}%
\author[2]{John Mugler}%
\author[2]{Craig Meyer}%
\author[2]{Eduard de Lange}%
\author[2]{Michael Shim}%
\author[2]{Kristin Wavell}%
\author[3]{Talissa Altes}%
\affil[1]{University of Virginia}%
\affil[2]{University of Virginia School of Medicine}%
\affil[3]{University of Missouri}%


\vspace{-1em}



  
  \date{May 08, 2024}


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\selectlanguage{english}
\begin{abstract}
Background: HHe-3 MR is a non-invasive imaging method which maps and
quantifies regions of ventilation heterogeneity (VH) in the lung. VH is
an important feature of asthma, but little is known as to how VH informs
patient phenotypes. Purpose: To determine if VH indicators quantified by
HHe-3 MRI predict phenotypic characteristics and map to regions of
inflammation in children with problematic wheeze/asthma. Methods. Sixty
children with poorly-controlled asthma underwent HHe-3 MRI, including 22
with bronchoalveolar lavage (BAL). The HHe-3 signal intensity defined
four ventilation compartments. The non-ventilated and hypoventilated
compartments divided by the total lung volume defined a VH index (VHI
\%). Results: Children with VHI \% in the upper quartile had
significantly greater airflow limitation, bronchodilator responsiveness,
blood eosinophils, expired nitric oxide (FeNO), and BAL eosinophilic/
neutrophilic granulocyte patterns compared to children with VHI \% in
the lower quartile. Lavage return from hypoventilated bronchial segments
had greater eosinophil \% than from ventilated segments. Conclusion: In
children with asthma, greater VHI \% as measured by HHe-3 MRI identifies
a severe phenotype with higher type 2 inflammatory markers, and maps to
regions of lung eosinophilia. Listed on ClinicalTrials.gov
(NCT02577497).%
\end{abstract}%



\sloppy


\textbf{Abbreviations}

BAL bronchoalveolar lavage

CT computerized tomography

FeNO Fraction expired nitric oxide

FEV\textsubscript{1} forced expired volume in one second

FEV\textsubscript{1}/FVC forced expired volume in one second/forced
vital capacity

FVC forced vital capacity

HHe-3 hyperpolarized helium-3

GINA Global Initiative for Asthma

ICS inhaled corticosteroids

LABA long-acting beta agonists

MCID Minimal clinically important difference

MR magnetic resonance

MRI magnetic resonance imaging

Vdef \% ventilation defect percent

VH ventilation heterogeneity

VHI \% ventilation heterogeneity index percent

VVI \% ventilated volume percent

\textbf{Author Contributions}

W. Gerald Teague, MD: Study design, senior clinician-investigator,
protocol development aind implementation, recruitment, clinical
oversight, data analysis.

Jaime Mata, PhD: Oversight of hyperpolarized gas preparation and
administration, technical leadership in administering gas and imaging
sequence protocols, day to day involvement in study conduct and
participant safety.

King Qing, PhD: Study design, technical co-leadership in administering
gas, oversight of imaging sequence protocols, day to day involvement in
study conduct and participant safety.

Nicholas J. Tustison, PhD: on-line image analysis, invented platform for
quantifiyng lung volume compartments based on on He-3 signal intensity.

John P. Mugler III PhD: Senior investigator for image development,
sequencing, and process, oversight of day to day image acquistion and
quality.

Craig H. Meyer, PhD: development of spiral pulse sequences and image
reconstruction.

Y. Michael Shim, MD: Medical leadership of hyperpolarized noble gas
research program, developed quality and safety standards, input on study
design.

Kristin Wavell: Lead study coordinator, responsible for study
adaptation, identification and intervention into episodes of poor asthma
control and exacerbations, central role in data acquisition and secure
storage, regulatory official.

Talissa Altes MD: Senior investigator, critical input into study design
and implementation.

\textbf{Introduction}

Inhaled hyperpolarized noble gases emit a signal detectable by MR which
maps the distribution of gas in the trachea-bronchial tree and regions
of gas exchange \textsuperscript{1-2}. In patients with asthma,
hyperpolarized gases distribute unevenly in the lungs. Regions with
dark, attenuated, He-3 signal are commonly referred to as ``ventilation
defects'' \textsuperscript{3-6}. Ventilation defects are attributed to
eosinophilic inflammatory debris and narrowing of the airways.
Ventilation defects increase in size with exercise and
methacholine-induced bronchoconstriction \textsuperscript{7-8}, and
decrease in size post-albuterol inhalation \textsuperscript{7,9}. Lung
regions with ventilation defects localize to regions of air trapping
mapped with multidetector CT in adults with asthma \textsuperscript{10}.
We previously reported that the ventilation defect \% (Vdef \%) was
greater in children with severe compared to mild asthma, and correlated
with poor symptom control and the magnitude of airflow limitation
measured with spirometry \textsuperscript{11}. In adults with severe
asthma, the Vdef \% positively predicted the number of past
exacerbations \textsuperscript{12}.

Although regional variations in the pattern of inflammation are likely
in asthma, little is known as to whether inflammed regions have greater
VH. Fain and colleagues \textsuperscript{10} found increased neutrophils
in BAL from lung regions with ventilation defects and air trapping. We
previously reported an adolescent with severe asthma wherein the
proximal bronchial segment to a lobe with ventilation defefects had
greater epithelial injury and infiltration of eosinophils compared to a
segment to a ventilated lobe \textsuperscript{13}. The Vdef\% decreases
following acute albuterol treatment in adults with asthma, but in the
sub-group with sputum eosinophilia, the improvement in VH is relatively
less \textsuperscript{14}. Mucus plugs identified by multidetector CT in
adults with asthma correspond to sputum eosinophilia and production of
eosinophil peroxidase-mediated oxidants \textsuperscript{15}. However,
studies based on sputum analysis are limited in so far as the precise
regional source of expectorated sputum cannot be identified.

To address these questions, a sample of children with problematic
wheeze/asthma underwent hyperpolarized He-3 (HHe-3) MRI. The
investigations had two purposes: 1) to study in cross-section whether
the magnitude of VH could differentiate phenotypic characteristics, and
2) whether areas of regional hypoventilation map to segments with
greater granulocyte infiltration.

\textbf{Methods}

The study sample included 60 children with treatment-refractory
wheeze/asthma referred to a university-based specialty clinic serving a
mixed urban-rural population in central Virginia. Enrollees underwent a
HHe-3 lung MRI within eight weeks of characterization procedures adapted
from the NIH/NHLBI Severe Asthma Research Program \textsuperscript{16}.
Participants were treated according to GINA
guidelines\textsuperscript{17} by an asthma specialist for a minimum of
three months before severity assignment \textsuperscript{18}. Details
regarding recruiting procedures and
characterization\textsuperscript{16}, treatment \textsuperscript{17,19},
and indications for bronchoscopy \textsuperscript{19} have been
published previously.

Inclusion criteria included ages 3-17 years, diagnosis of problematic
wheeze (n = 11) or confirmed asthma (n= 49) based on change in
FEV\textsubscript{1}\% [?] 12\% from baseline post-bronchodilator (BD),
and/or a previous positive methacholine bronchoprovocation test, and
treatment for a minimum of three months with [?]1 asthma controllers.
Inadequate control was defined according to an asthma control test
(ACT/cACT) \textless{}20, 2 or more exacerbations in the year prior to
enrollment, and/or persistent airflow limitation
(FEV\textsubscript{1}/FVC \textless{} 90\textsuperscript{th} \%
predicted) \textsuperscript{20}. Exclusion criteria included premature
birth \textless{} 36 weeks gestation, inability to cooperate with the
MRI procedures, and significant non-asthmatic diagnoses including
cardiac disease, cystic fibrosis, and a documented lower respiratory
infection within six weeks of the enrollment visit. Study participation
required informed consent and protocols were approved by the University
of Virginia Institutional Revew Board (IRB\# 157200 and \#18422). The
study was listed on ClinicalTrials.gov (NCT02577497).

\emph{Hyperpolarized Helium-3 Lung MRI Procedures}

Children underwent a standard imaging protocol with safety monitoring
under IND 57866. Images were obtained without sedation using a 1.5-T
commercial whole-body scanner (Avanto, Siemens Medical Solutions,
Malvern PA) and either a flexible, vest-shaped chest radio frequency
(RF) coil (Clinical MR Solutions, Brookfield, WI) or a fixed geometry RF
coil (Rapid Biomedical, Rimpar, Germany) tuned to the He-3 resonant
frequency. Details of the MR acquisition procedures have been published
previously \textsuperscript{11} and are described in detail in the
E-Supplement methods.

\emph{Bronchoscopy and BAL Procedures}

Twenty-two children with therapy-resistant, inadequately-controlled
asthma had clinically-indicated bronchoscopy with bronchoalveolar lavage
(BAL) and assessment of air space and blood inflammatory markers two
weeks following HHe-3 MRI. Samples were shared between the clinical and
research laboratories under protocols approved by the University of
Virginia Institutional Review Board (IRB \# 17555, IRB \# 19180, and IRB
\# 10905). A detailed description of the clinical pathway and methods
for bronchoscopy and BAL has been published
previously\textsuperscript{19}.

To compare granulocyte constituents in BAL from lung segments with and
without visible ventilation defects, 13 children underwent MR
image-guided BAL in bronchial segments to lobes with and without visible
ventilation defects. The images were reviewed by a pediatric radiologist
(TAA) in advance, lobes with and without ventilation defects were
identified for BAL in the main bronchial segments or sub-segments
accordingly. Fresh BAL was submitted to the cytopathology laboratory and
examined for total and differential cell count using manual procedures.
Paired BAL aliquots were labeled 1 and 2 for cytospin preparation of
smears for differential cell counts, done in triplicate, by a
cytopathologist blinded to the ventilation status of the segment from
which the sample was obtained. Safety of the bronchoscopy procedures has
been reported previously with no unexpected major adverse
events\textsuperscript{19, 22}.

\emph{Data Analysis}

Four volume compartments were defined from the formatted gray-scale MRI
images according to a previously published analysis platform (see
E-supplement) \textsuperscript{11, 21}. VH indicators included the Vdef
\% (non-ventilated volume/total lung volume), and the VHI \%
(non-ventilated +hypoventilated volume/total lung volume).

To examine whether the magnitude of VH informed clinical features, the
sample was stratified into three sub-groups according to the quartile
distribution of the VHI \%. Sub-group one, mild VH, was \textless{}
25\textsuperscript{th} \%ile VHI \%, sub-group two, moderate VH, middle
25\textsuperscript{th} -75\textsuperscript{th} \%ile, and sub-group
three, severe VH, was \textgreater{} 75\textsuperscript{th} \%ile.
Between sub-group comparisons among scaled and categorical variables are
described in the E-supplement. BAL granulocyte patterns were defined as
isolated eosinophilia, isolated neutrophilia, mixed granulocytic, and
pauci-granuolocytic based on published criteria \textsuperscript{19,
23}. A p value of \textless{} .05 was used to refute the null
hypothesis.

\textbf{Results}

Sixty children had detailed characterizations with MRs, including 22 who
underwent diagnostic bronchoscopy. The mean sample age was 9.9 \selectlanguage{ngerman}± 3.9
years (Table I). Most were male (63\%), 1/2 reported non-white
racial/ethnic backgrounds. Seventy-five \% had cACT/ACT scores \selectlanguage{english}[?] 19,
51\% had \selectlanguage{english}[?] 1 asthma-related hospital admissions in the past year. More
than 84\% reported treatment with \selectlanguage{english}[?] 2 asthma controller medications,
50\% with ICS doses \selectlanguage{english}[?] 800 mcg/day fluticasone equivalents. A pre-BD
FEV\textsubscript{1}/FVC \% \textless{} 90\%, was found in 47\%.
Increased serum IgE to \selectlanguage{english}[?] 1 allergens was detected in 80\%, and 60\% were
sensitized to \selectlanguage{english}[?] 4 allergens. Eosinophilia, defined by \selectlanguage{english}[?] 300
eosinophils/ul blood, was present in 50\%.

\emph{HHe-3 MRI Lung Volume Compartments and VH Indicators}

For the total sample (n=60) the four volume compartments (E-supplement
Table E-1) included the non-ventilated volume (2.8 \% total volume),
hypoventilated volume (16.4 \% total volume), ventilated volume (27.8\%
total volume) and well-ventilated volume (53\% total volume). Indices of
VH included the Vdef \% (1.29 +- 3.13), the VHI \%, (17.59 +- 13.36) and
the VVI \% (82.40 +- 13.36). The VHI \% and VVI \% had Gaussian
distributions, but not the Vdef \% (E-supplement Figure E-1).

To examine whether volume sub-compartments varied significantly in
children with greater VH, sub-volumes were compared according to the
distribution of the VHI \% (Figure 1). The non-ventilated and
hypoventilated compartments were significantly higher, whereas the
well-ventilated compartment was significantly lower, in children with
VHI \% values in the upper 25\textsuperscript{th} \%ile compared to the
lower 25\textsuperscript{th} \%ile and the middle
25\textsuperscript{th}-75\textsuperscript{th} \%iles. Thus, greater VH
was accompanied by greater non-ventilated and hypoventilated lung
volumes, lower well-ventilated volume, but no significant change in the
ventilated volume compartment.

\emph{Phenotypic Features Compared According to VHI \% Quartiles}

Children with VHI \% in the upper quartile had phenotypic features
unique from those in children in the lower quartile (Table I and Figure
2). Children with VHI \% in the upper 75\textsuperscript{th} \%ile had
greater non-white racial/ethnic backgrounds (73\% vs 20\%, p = .006),
more lifetime ICU admissions (range of 0-6 vs 0-4, p = .04), and were
treated with twice the number of daily controller medications (4.0 vs
2.0 , p = .02) compared to children in the lower
25\textsuperscript{th}\%ile.

Accordingly, children with VHI \% in the upper
75\textsuperscript{th}\%ile had reduced lung function with greater
airflow limitation and bronchodilator responsiveness compared to
children in the lower 25\textsuperscript{th} \%ile (Table I).
Differences included lower pre-BD FEV\textsubscript{1} \% (80 vs 100, p
= .02), and lower pre-BD FEV\textsubscript{1}/FVC \% (83 vs 94, p =
.04) in children with the upper 25\textsuperscript{th} \%ile VHI \%.
Both the pre- and post-BD FEF\textsubscript{25-75} \% (55 vs 89 and 61
vs 91, respectively, p \textless{} .05 for both) were less than
mid-flows in children with VHI \% in the lower 25\textsuperscript{th}
\%ile. Furthemore children with VHI \% in the upper
75\textsuperscript{th} \%ile had overall greater bronchodilator
reversibility, and the \% change in the FEV\textsubscript{1} \% from
baseline was higher in the 75th versus
25\textsuperscript{th}-75\textsuperscript{th} \%iles (22 vs 11, p =
.01).

VHI \% sub-groups likewise had difference in the magnitude of type 2
inflammatory markers (Table I). Children with VHI \% in the
75\textsuperscript{th} \%ile had higher absolute eosinophil counts (620
cells/ ul vs 220 cells/ ul blood, p = .001), a higher proportion with
absolute eosinophil counts \selectlanguage{english}[?] 300 cells/ul blood (87\% versus 20\%, p =
.001) and higher FeNO (36 ppb vs 22 ppb, p = .03) compared to lower
\%iles. VHI \% sub-groups did not differentiate total IgE and the number
of positive specific IgE tests. Overall correlations between VH
indicators and scaled outcomes were modest to poor (See E-supplement,
results and Table E-2).

\emph{BAL Constituents}

BAL total cell count, \% eosinophils and \% neutrophils were not
significantly different among the VHI \% sub-groups (Table II). However
categorical granulocyte patterns did vary significantly. The proportion
of children with pauci-granulocytic BAL was lower, 17\%, in upper
75\textsuperscript{th} \%ile VHI \% than it was in the the
25\textsuperscript{th}-75\textsuperscript{th} \%ile (67\%) and the
25\textsuperscript{th} \%ile (75\%, p = .04).

In 13 children who underwent paired image-directed BALs, eosinophil
counts/100 cells (Figure 3) were significantly higher (p = .04) in BAL
from bronchial segments in lung regions with visible ventilation defects
(7 +- 9 \%) compared to regions without visible ventilation defects (3 +-
2 \%). There was no difference in the percentage of BAL macrophages,
lymphocytes, or neutrophils between lobes with and without ventilation
defects. There were no significant differences among VHI \% sub-groups
in the presence of pathogenic bacteria or viruses (Table II, and E-
Supplement, results).

\textbf{Discussion}

Children with problematic wheeze/asthma and significant VH, identified
by VHI \% in the upper 75\textsuperscript{th} \%ile, had a severe
clinical phenotype with greater airflow limitation, bronchodilator
reversibiity, and markers of type 2 inflammation. BAL from bronchial
segments to lobes with ventilation defects had greater eosinophils, and
children with VHI \% in the upper 75\textsuperscript{th} \%ile
accordingly had greater eosinophilic and neutrophilic BAL granulocyte
patterns compared to children in the lower 25\textsuperscript{th} \%ile.
These results indirectly support an important role of eosinophilic
debris and type 2 inflammations in the formation of regions of
hypoventilation in asthma. The results also show that the VHI \%, which
defines both the non- and hypoventilated volume compartments in asthma,
is likely a better predictor of disease severity in asthma compared to
the traditional indicator, the Vdef \%.

Original studies in patients with asthma based on hyperpolarized gas MRI
used ventilation defect counts as estimates of
VH\textsuperscript{3-4,6-7}. Recently, analytic
platforms\textsuperscript{5,11-12,14} were developed which quantified
the Vdef \% as a fraction of the total lung volume. In a previous
report\textsuperscript{11} in children with moderate to severe asthma,
the median Vdef \% was 1.3\%, identical to the Vdef \% in the present
study. In this and previous reports, the Vdef \% is skewed towards
smaller values in a non-Gaussian distribution; hence we substituted the
VHI \% as an alternate VH metric to differentiate clinical features in
the present study. The VHI \% is normally distributed and overall
performed better than the Vdef \% as a predictor of clinical outcomes.
However, both the VHI \% and the Vdef \% are global indicators of net VH
in the lung, and vary significantly by anatomic region. A limiting
factor in using total lung VH as a primary outcome to test treatment
effects and exacerbations is insensitivity to regional differences in
response which could be missed by a total lung indicator.

The results of the present study are among the first that we can find
which resolve localized patterns of lung granulocytic inflammation in
asthmatics based on visible ventilation defects. BAL return from lung
lobes with ventilation defects had greater eosinophils. These results
diverge slightly from those of Fain et al based on analysis of regional
air trapping and BAL constituents in adults with
asthma\textsuperscript{10}. In that study, the absolute number and
percentage of BAL neutrophils correlated with lung defect volume. The
recent findings of Dunican et al based on CT identify a relationship
between luminal obstruction with mucus plugs and sputum eosinophilia in
adults with asthma \textsuperscript{15}.

The present study sample has co-morbid features which limits its
generalizability to a broad asthma population. We would expect that the
degree of VH in a community-based sample might be less than in the
present study, enriched in children with severe asthma and inadequate
symptom control. We studied a relatively young sample, whereby past
studies have shown greater VH in older patients with
asthma\textsuperscript{5}. We therefore would recommend future studies
using hyperpolarized noble gas imaging with uniform image acquisition
sequences at controlled lung volumes at several centers. This has been
done in a limited way with testing the effects of bronchial thermoplasty
on VH in asthma with promising early results \textsuperscript{24}.

\textbf{Acknowledgements}

The authors wish to recognize the children and their families who
frequently traveled some distance to undergo the study procedures.
Likewise we wish to recognize the expertise of the study coordinators,
particularly Theresa Altherr, Denise Thompson-Batt, and Joanne Cassani.

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21.Tustison NJ, Avants BB, Flors L, Altes TA, de Lange EE, Mugler JP
3rd, Gee JC. Ventilation-based segmentation of the lungs using
hyperpolarized (3) He MRI. \emph{J Magn Reson Imaging} 2011; 34: 831-41.

22. Wisniewski JA, Muehling LM, Eccles JD, Agrawal R, Capaldo BJ,
Shirley DA, Patrie JT, Workman L, Lawrence MG, Teague WG, Woodfolk JA.
TH1 signatures are present in the lower airways of children with severe
asthma, regardless of allergic status. J Allergy Clin Immunol 2018;141
(6): 2048-2060.

23.de Blic J, Midulla F, Barbato A, Clement A, Dab I, Eber E, et al, for
the ERS Task Force on Bronchoalveolar Lavage in Children. \emph{Eur
Respir J} 2000; 15:217-31.

24. Thomen RP, Sheshadri A, Quirk JD, Kozlowski J, Ellison HD,
Szczesniak RD, Castro M, Woods JC. Regional ventilation changes in
severe asthma after bronchial thermoplasty with 3He MR imaging and
CT.\emph{Radiology} 2015; 274: 250-259.

\textbf{Tables}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
Table I Features of Children with Problematic Wheeze/Asthma Compared
According to VHI \% Dispersion & Table I Features of Children with
Problematic Wheeze/Asthma Compared According to VHI \% Dispersion &
Table I Features of Children with Problematic Wheeze/Asthma Compared
According to VHI \% Dispersion & Table I Features of Children with
Problematic Wheeze/Asthma Compared According to VHI \% Dispersion &
Table I Features of Children with Problematic Wheeze/Asthma Compared
According to VHI \% Dispersion\tabularnewline
\midrule
\endhead
& Mild VH 25\textsuperscript{th} \%ile n=15 & Moderate VH
25\textsuperscript{th}-75\textsuperscript{th} \%ile n=30 & Severe VH
75\textsuperscript{th} \%ile n=15 & Total n=60\tabularnewline
Age (years) \selectlanguage{greek}\textsuperscript{α} & 10.6 \selectlanguage{ngerman}± 3.5 & 9.1 \selectlanguage{ngerman}± 3.9 & 11.1 \selectlanguage{ngerman}± 4.3 &
9.9 \selectlanguage{ngerman}± 3.9\tabularnewline
Asthma Duration (years) & 7.4 \selectlanguage{ngerman}± 2.8 & 6.1 \selectlanguage{ngerman}± 4.4 & 8.3 \selectlanguage{ngerman}± 3.9 & 6.9 \selectlanguage{ngerman}±
4.0\tabularnewline
Male sex n (\%) ** & 11 (73) & 18 (60) & 9 (60) & 38 (63)\tabularnewline
Non-white race n (\%) & 3 (20) & 16 (53) & 11 (73) \selectlanguage{greek}\textsuperscript{Ϯ} &
30 (50)\tabularnewline
Body Mass Index (kg/m\textsuperscript{2}) & 20.2 \selectlanguage{ngerman}± 3.3 & 21.3 \selectlanguage{ngerman}± 6.4 &
21.6 \selectlanguage{ngerman}± 6.5 & 21.1 \selectlanguage{ngerman}± 5.8\tabularnewline
BMI \% predicted & 75 \selectlanguage{ngerman}± 18 & 74 \selectlanguage{ngerman}± 27 & 64 \selectlanguage{ngerman}± 40 & 72 \selectlanguage{ngerman}± 29\tabularnewline
Obese n (\%) & 3 (20) & 12 (40) & 6 (40) & 21 (35)\tabularnewline
ACT/cACT & 18 \selectlanguage{ngerman}± 4 & 15 \selectlanguage{ngerman}± 4 & 14 \selectlanguage{ngerman}± 4 \selectlanguage{english}\textsuperscript{[?]} & 16 \selectlanguage{ngerman}±
5\tabularnewline
Hospital Admissions & 0 \selectlanguage{ngerman}± 1 & 0 \selectlanguage{ngerman}± 2 & 1 \selectlanguage{ngerman}± 5 \selectlanguage{greek}\textsuperscript{µ} & 1 \selectlanguage{ngerman}±
2\tabularnewline
ICU Admissions & 0 (0-1) & 0 (0-2) & 0 (0-6) \selectlanguage{greek}\textsuperscript{ϴ} & 0
(0-6)\tabularnewline
\# Controller Meds & 2 \selectlanguage{ngerman}± 1 & 2 \selectlanguage{ngerman}± 1 & 4.0 \selectlanguage{ngerman}± 2 \selectlanguage{romanian}\textsuperscript{Ɣ} & 3 \selectlanguage{ngerman}±
1\tabularnewline
Daily ICS Dose & 400 \selectlanguage{ngerman}± 640 & 460 \selectlanguage{ngerman}± 520 & 800 \selectlanguage{ngerman}± 460 & 640 \selectlanguage{ngerman}±
480\tabularnewline
Pre-BD FEV\textsubscript{1} \% & 100 \selectlanguage{ngerman}± 12 & 93 \selectlanguage{ngerman}± 17 & 80 \selectlanguage{ngerman}± 28
\selectlanguage{greek}\textsuperscript{β} & 91 \selectlanguage{ngerman}± 20\tabularnewline
Post-BD FEV\textsubscript{1} \% & 111 \selectlanguage{ngerman}± 10 & 101 \selectlanguage{ngerman}± 21 & 90 \selectlanguage{ngerman}± 27
\selectlanguage{greek}\textsuperscript{Ω} & 99 \selectlanguage{ngerman}± 23\tabularnewline
\selectlanguage{english}[?] FEV\textsubscript{1} \% post-BD & 15 \selectlanguage{ngerman}± 24 & 11 \selectlanguage{ngerman}± 10 & 22 \selectlanguage{ngerman}± 12
\textsuperscript{¥} & 15 \selectlanguage{ngerman}± 15\tabularnewline
Pre-BD FVC \% & 108 \selectlanguage{ngerman}± 10 & 103 \selectlanguage{ngerman}± 14 & 97 \selectlanguage{ngerman}± 25 & 103 \selectlanguage{ngerman}± 17\tabularnewline
Post-BD FVC \% & 117 \selectlanguage{ngerman}± 2 & 106 \selectlanguage{ngerman}± 16 & 102 \selectlanguage{ngerman}± 27 & 107 \selectlanguage{ngerman}± 20\tabularnewline
\selectlanguage{english}[?] FVC \% post-BD & 2 \selectlanguage{ngerman}± 6 & 2 \selectlanguage{ngerman}± 5 & 8 \selectlanguage{ngerman}± 9 \selectlanguage{greek}\textsuperscript{Ω} & 4 \selectlanguage{ngerman}±
7\tabularnewline
Pre-BD FEV\textsubscript{1}/FVC \% & 94 \selectlanguage{ngerman}± 11 & 89 \selectlanguage{ngerman}± 11 & 83 \selectlanguage{ngerman}± 12
\selectlanguage{greek}\textsuperscript{ϴ} & 89 \selectlanguage{ngerman}± 12\tabularnewline
Post-BD FEV\textsubscript{1}/FVC \% & 96 \selectlanguage{ngerman}± 9 & 95 \selectlanguage{ngerman}± 11 & 90 \selectlanguage{ngerman}± 13 & 93
\selectlanguage{ngerman}± 11\tabularnewline
Pre-BD FEF\textsubscript{25-75} \% & 89 \selectlanguage{ngerman}± 26 & 76 \selectlanguage{ngerman}± 34 & 55 \selectlanguage{ngerman}± 33
\selectlanguage{greek}\textsuperscript{β} & 74 \selectlanguage{ngerman}± 34\tabularnewline
Post-BD FEF\textsubscript{25-75} \% & 91 \selectlanguage{ngerman}± 33 & 94 \selectlanguage{ngerman}± 43 & 61 \selectlanguage{ngerman}± 35
\selectlanguage{greek}\textsuperscript{Ω} & 83 \selectlanguage{ngerman}± 41\tabularnewline
Geometric Mean Total IgE (IU/ml) & 174 (24-4804) & 151 (1-3638) & 385
\selectlanguage{greek}\textsuperscript{κ} \selectlanguage{english}(47-2047) & 197 (1-4804)\tabularnewline
\# + specific IgE tests \textsuperscript{[?]} & 3 \selectlanguage{ngerman}± 7 & 4 \selectlanguage{ngerman}± 11 & 6 \selectlanguage{ngerman}± 8 & 5
\selectlanguage{ngerman}± 8\tabularnewline
Highly Sensitized n (\%) & 7 (47) & 17 (57) & 12 (80) & 36
(60)\tabularnewline
Absolute Blood Eosinophils (cells/\selectlanguage{greek}µ\selectlanguage{english}l) \selectlanguage{greek}\textsuperscript{α} & 220 \selectlanguage{ngerman}± 180 &
285 \selectlanguage{ngerman}± 440 & 620 \selectlanguage{ngerman}± 660 \selectlanguage{greek}\textsuperscript{λ} & 447 \selectlanguage{ngerman}± 403\tabularnewline
Blood Eosinophilia (\selectlanguage{english}[?] 300 cells/\selectlanguage{greek}µ\selectlanguage{english}l) n (\%) & 3 (20) & 14 (47) & 13 (87)
++ & 30 (50)\tabularnewline
Expired NO (ppb) & 22 \selectlanguage{ngerman}± 11 & 19 \selectlanguage{ngerman}± 11 & 36 \selectlanguage{ngerman}± 18 \selectlanguage{greek}\textsuperscript{π} & 23
\selectlanguage{ngerman}± 14\tabularnewline
\selectlanguage{greek}α \selectlanguage{english}mean \selectlanguage{ngerman}± SD; ** column \%; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .006, [?] p = .09 compared to mild VH; u
p =.06; \selectlanguage{greek}ϴ \selectlanguage{english}p = .04 compared to mild VH; \selectlanguage{romanian}Ɣ p = .02; \selectlanguage{greek}β \selectlanguage{english}p = .02 compared to
mild VH; \selectlanguage{greek}Ω \selectlanguage{english}p = .08 compared to mild; \selectlanguage{ngerman}¥ p = .01 compared to moderate VH;
\selectlanguage{greek}κ \selectlanguage{english}p = .08 compared to moderate VH. \selectlanguage{greek}λ \selectlanguage{english}p = .001 compared to mild and
moderate VH. \selectlanguage{greek}ϮϮ \selectlanguage{english}p = .001. \selectlanguage{greek}π \selectlanguage{english}p = .03 compared to moderate VH. & \selectlanguage{greek}α \selectlanguage{english}mean \selectlanguage{ngerman}±
SD; ** column \%; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .006, [?] p = .09 compared to mild VH; u p =.06; \selectlanguage{greek}ϴ
\selectlanguage{english}p = .04 compared to mild VH; \selectlanguage{romanian}Ɣ p = .02; \selectlanguage{greek}β \selectlanguage{english}p = .02 compared to mild VH; \selectlanguage{greek}Ω
\selectlanguage{english}p = .08 compared to mild; \selectlanguage{ngerman}¥ p = .01 compared to moderate VH; \selectlanguage{greek}κ \selectlanguage{english}p = .08
compared to moderate VH. \selectlanguage{greek}λ \selectlanguage{english}p = .001 compared to mild and moderate VH. \selectlanguage{greek}ϮϮ
\selectlanguage{english}p = .001. \selectlanguage{greek}π \selectlanguage{english}p = .03 compared to moderate VH. & \selectlanguage{greek}α \selectlanguage{english}mean \selectlanguage{ngerman}± SD; ** column
\%; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .006, [?] p = .09 compared to mild VH; u p =.06; \selectlanguage{greek}ϴ \selectlanguage{english}p = .04
compared to mild VH; \selectlanguage{romanian}Ɣ p = .02; \selectlanguage{greek}β \selectlanguage{english}p = .02 compared to mild VH; \selectlanguage{greek}Ω \selectlanguage{english}p = .08
compared to mild; \selectlanguage{ngerman}¥ p = .01 compared to moderate VH; \selectlanguage{greek}κ \selectlanguage{english}p = .08 compared
to moderate VH. \selectlanguage{greek}λ \selectlanguage{english}p = .001 compared to mild and moderate VH. \selectlanguage{greek}ϮϮ \selectlanguage{english}p =
.001. \selectlanguage{greek}π \selectlanguage{english}p = .03 compared to moderate VH. & \selectlanguage{greek}α \selectlanguage{english}mean \selectlanguage{ngerman}± SD; ** column \%; \selectlanguage{greek}Ϯ
\selectlanguage{english}p = .006, [?] p = .09 compared to mild VH; u p =.06; \selectlanguage{greek}ϴ \selectlanguage{english}p = .04 compared to
mild VH; \selectlanguage{romanian}Ɣ p = .02; \selectlanguage{greek}β \selectlanguage{english}p = .02 compared to mild VH; \selectlanguage{greek}Ω \selectlanguage{english}p = .08 compared to
mild; \selectlanguage{ngerman}¥ p = .01 compared to moderate VH; \selectlanguage{greek}κ \selectlanguage{english}p = .08 compared to moderate
VH. \selectlanguage{greek}λ \selectlanguage{english}p = .001 compared to mild and moderate VH. \selectlanguage{greek}ϮϮ \selectlanguage{english}p = .001. \selectlanguage{greek}π \selectlanguage{english}p = .03
compared to moderate VH. & \selectlanguage{greek}α \selectlanguage{english}mean \selectlanguage{ngerman}± SD; ** column \%; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .006, [?] p =
.09 compared to mild VH; u p =.06; \selectlanguage{greek}ϴ \selectlanguage{english}p = .04 compared to mild VH; \selectlanguage{romanian}Ɣ p =
.02; \selectlanguage{greek}β \selectlanguage{english}p = .02 compared to mild VH; \selectlanguage{greek}Ω \selectlanguage{english}p = .08 compared to mild; \selectlanguage{ngerman}¥ p =
.01 compared to moderate VH; \selectlanguage{greek}κ \selectlanguage{english}p = .08 compared to moderate VH. \selectlanguage{greek}λ \selectlanguage{english}p =
.001 compared to mild and moderate VH. \selectlanguage{greek}ϮϮ \selectlanguage{english}p = .001. \selectlanguage{greek}π \selectlanguage{english}p = .03 compared
to moderate VH.\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllllll@{}}
\toprule
\begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage} & \begin{minipage}[b]{0.05\columnwidth}\raggedright\strut
Table II BAL Constituents Compared According to VHI \% Dispersion\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell and Granulocyte Counts\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Constituent\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Constituent\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Constituent\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Mild VH 25\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Mild VH 25\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Mild VH 25\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Mod. VH 25\textsuperscript{th}-75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Mod. VH 25\textsuperscript{th}-75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Severe VH 75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Severe VH 75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Severe VH 75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Total\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Total\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Sample n\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Sample n\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Sample n\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
22\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
22\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell Count (X 10\textsuperscript{6} )\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell Count (X 10\textsuperscript{6} )\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total Cell Count (X 10\textsuperscript{6} )\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.44 \selectlanguage{ngerman}± 1.44\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.44 \selectlanguage{ngerman}± 1.44\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.44 \selectlanguage{ngerman}± 1.44\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.47 \selectlanguage{ngerman}± 3.62\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.47 \selectlanguage{ngerman}± 3.62\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.14 \selectlanguage{ngerman}± 2.35\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.14 \selectlanguage{ngerman}± 2.35\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.14 \selectlanguage{ngerman}± 2.35\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.17 \selectlanguage{ngerman}± 1.58\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1.17 \selectlanguage{ngerman}± 1.58\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Eosinophils (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Eosinophils (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Eosinophils (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 2\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 2\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 2\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 \selectlanguage{ngerman}± 8\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 \selectlanguage{ngerman}± 8\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 \selectlanguage{ngerman}± 8\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 2\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
BAL eosinophils \selectlanguage{english}[?] 1\% n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
BAL eosinophils [?] 1\% n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
BAL eosinophils [?] 1\% n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 (50)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 (50)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 (50)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
6 (27)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
6 (27)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Neutrophils (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Neutrophils (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Neutrophils (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 \selectlanguage{ngerman}± 4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 \selectlanguage{ngerman}± 4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 \selectlanguage{ngerman}± 4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 \selectlanguage{ngerman}± 15\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 \selectlanguage{ngerman}± 15\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15 \selectlanguage{ngerman}± 32\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15 \selectlanguage{ngerman}± 32\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15 \selectlanguage{ngerman}± 32\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 \selectlanguage{ngerman}± 18\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 \selectlanguage{ngerman}± 18\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
BAL neutrophils \selectlanguage{english}[?] 6 \% n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
BAL neutrophils [?] 6 \% n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
BAL neutrophils [?] 6 \% n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 (67)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 (67)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 (67)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (36)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (36)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lymphocytes (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lymphocytes (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lymphocytes (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 \selectlanguage{ngerman}± 3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 \selectlanguage{ngerman}± 3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 \selectlanguage{ngerman}± 3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 \selectlanguage{ngerman}± 4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 \selectlanguage{ngerman}± 4\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 \selectlanguage{ngerman}± 8\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 \selectlanguage{ngerman}± 8\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 \selectlanguage{ngerman}± 8\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 \selectlanguage{ngerman}± 3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 \selectlanguage{ngerman}± 3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Macrophages (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Macrophages (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Macrophages (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
68 \selectlanguage{ngerman}± 26\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
68 \selectlanguage{ngerman}± 26\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
68 \selectlanguage{ngerman}± 26\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
72 \selectlanguage{ngerman}±32\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
72 \selectlanguage{ngerman}±32\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
58 \selectlanguage{ngerman}± 40\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
58 \selectlanguage{ngerman}± 40\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
58 \selectlanguage{ngerman}± 40\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
68 \selectlanguage{ngerman}± 37\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
68 \selectlanguage{ngerman}± 37\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Epithelial cells (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Epithelial cells (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Epithelial cells (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21 \selectlanguage{ngerman}± 25\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21 \selectlanguage{ngerman}± 25\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21 \selectlanguage{ngerman}± 25\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
12 \selectlanguage{ngerman}± 23\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
12 \selectlanguage{ngerman}± 23\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21 \selectlanguage{ngerman}± 23\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21 \selectlanguage{ngerman}± 23\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21 \selectlanguage{ngerman}± 23\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
20 \selectlanguage{ngerman}± 25\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
20 \selectlanguage{ngerman}± 25\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Granulocyte Categories *\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Isolated Eosinophilia\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Isolated Eosinophilia\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Isolated Eosinophilia\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1(17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1(17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1(17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (9)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Isolated Neutrophilia\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Isolated Neutrophilia\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Isolated Neutrophilia\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (33)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (33)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (33)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 (18)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Mixed Granulocytic\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Mixed Granulocytic\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Mixed Granulocytic\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (33)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (33)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (33)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 (18)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Pauci-granulocytic\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Pauci-granulocytic\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Pauci-granulocytic\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 (75)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
3 (75)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (67)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (67)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (67)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (67)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (17) \selectlanguage{greek}\textsuperscript{Ϯ}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (17) \selectlanguage{greek}\textsuperscript{Ϯ}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (17) \selectlanguage{greek}\textsuperscript{Ϯ}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
12 (54)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Potential Lower Respiratory Pathogens \selectlanguage{greek}\textsuperscript{α}\selectlanguage{english}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
25\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
25\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
25\textsuperscript{th}-75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
25\textsuperscript{th}-75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
25\textsuperscript{th}-75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
75\textsuperscript{th} \%ile\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Total\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Sample n\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Sample n\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
11\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
11\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
21\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
41\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
41\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
41\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Pathogenic bacteria n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Pathogenic bacteria n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (9)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
1 (9)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (38)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (38)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
8 (38)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (22)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (22)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (22)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
11 (27)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
11 (27)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
11 (27)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
+ Virus PCR n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
+ Virus PCR n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 (36)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
4 (36)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
9 (43)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
9 (43)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
9 (43)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (22)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (22)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
2 (22)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15 (37)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15 (37)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
15 (37)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
+ Bacteria/viruses\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
+ Bacteria/viruses\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 (24) **\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 (24) **\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 (24) **\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 (12)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 (12)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
5 (12)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Lipid Laden Macrophage Index (range 0-5)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
Median\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 3\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
0 \selectlanguage{ngerman}± 0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
References \textsuperscript{19,23}; isolated eosinophilia \selectlanguage{english}[?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia \selectlanguage{english}[?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic \selectlanguage{english}[?] 6\%
neutrophils and \selectlanguage{english}[?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage} & \begin{minipage}[t]{0.05\columnwidth}\raggedright\strut
*References \textsuperscript{19,23}; isolated eosinophilia [?] 1\%
eosinophils, and \textless{} 6\% neutrophils; isolated neutrophilia [?]
6\% neutrophils and 0\% eosinophils; mixed granulocytic [?] 6\%
neutrophils and [?] 1\% eosinophils; pauci-granulocytic \textless{} 6\%
neutrophils and 0\% eosinophils; \selectlanguage{greek}Ϯ \selectlanguage{english}p = .04; \selectlanguage{greek}α \selectlanguage{english}bacteria are
\emph{Streptococcus} \emph{pneumoniae}, \emph{Hemophilus}
\emph{influenzae}, and \emph{Moraxella} \emph{catarrhalis}; viruses are
\emph{Enteroviradae}/\emph{HRV}, \emph{Human metapneumovirus}, and
\emph{Parainfluenza} \emph{II}; ** p = .05.\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Figure Legends}

Figure 1. Violin plots showing the probability distribution of lung
volumes according to the quartile distribution of the VHI \% in children
with problematic wheeze/asthma. In A), the non-ventilated compartment
was significantly greater in children with VHI \% in the upper quartile,
and in B) the hypoventilated compartment likewise was significantly
higher. In C) the ventilated compartment volume was not significantly
different among the VHI \% quartiles, however in D) the well-ventilated
compartment was significantly lower in children with VHI \% in the upper
quartile compared to children with VHI \% in the lower quartile.

Figure 2. Representative HHe-3 images from children with mild, moderate,
and severe ventilation heterogeneity. The VHI \% located below each
image was derived from the non-ventilated and hypoventilated volume
divided by the total lung volume. Regional maps of the lung volume
compartments are indicated by a color labeling algorithm. The table
compares phenotypic features that were significantly (p \textless{} .05)
different in children with VHI \% in the upper quartile compared to
children in the lower quartile.

Figure 3. Within subject analysis of granulocyte counts/hpf in BAL
return from ventilated and non-ventilated lung regions in 13 children
with asthma. Ventilation status of a lung region was determined
according to the presence or absence of visible ventilation defects on
HHe-3 lung MRI. The plots are probability density functions and paired
counts of A) macrophage, B) lymphocyte, C) eosinophil, and D) neutrophil
numbers according to regional ventilation status.

\textbf{Figures}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure 1.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Figure 2.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Figure 3.

\selectlanguage{english}
\FloatBarrier
\end{document}

