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579

Index

ACE inhibitorscough induction 189–90, 557, 560, 571–2fibrotic lung disease treatment 348

Acinetobacter 367, 368, 382drug resistance 371

activator protein-1 (AP-1) 33, 35, 226corticosteroid resistance and 49–50

acute interstitial pneumonia (AIP) 249, 258–9treatment 259

acute respiratory distress syndrome (ARDS) 259adenocarcinoma 519, 520

see also lung canceradenosine, pulmonary hypertension investigation 481–2adenovirus 364adhesion molecules 36

corticosteroid effects 36adrenaline 56–7, 61adult respiratory distress syndrome (ARDS) 504air conditioner lung 286airway hyperresponsiveness (AHR) 6

�2-agonist effects 74long-term treatment 79–80

corticosteroid effects 38leukotriene importance 126potassium channel opener effects 177–9

airway nervespotassium channel openers 176–7remodelling 22

airway plugging, asthma 6airway smooth muscle see bronchial smooth muscleairway vessel remodelling see remodellingairway wall innervation 22airway wall thickening see remodellingallele specific mutations (ASM) 526–7allergen-induced asthma 128–9allergic responses 119allergy 141–2

Cambridge University Press978-0-521-77321-8 - Drugs for the Treatment of Respiratory DiseasesEdited by Domenico Spina, Clive P. Page, William J.Metzger and Brian J. O’ConnorIndexMore information

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alpha-antitrypsin 430, 431alveolar phospholipidosis 311alveolitis, extrinsic allergic 286–9

see also cryptogenic fibrosing alveolitis (CFA); fibrosingalveolitis (FA)

amikacin 439, 442aminoglycosides

chronic bronchial suppuration treatment 417cystic fibrosis management 439–40, 441

aminophylline 155amiodarone, pulmonary toxicity 269amlexanox 122amlodipine, pulmonary hypertension treatment 485, 487amoxicillin

chronic bronchial suppuration treatment 420cystic fibrosis management 436pneumonia treatment 379

ampicillinpneumonia treatment 379resistance 370

amrinone 147amyloidosis 316–17ANCA-associated vasculitides 298–9angiogenesis 507–8

asthma 20inhibition of 508

metalloproteinase inhibitors 508pulmonary hypertension and 507–8

angiomyolipomas 309–10angiostatin 508angiotensin II receptor antagonists 572

fibrotic lung disease treatment 348anti-lipid A antibiotics 390antiarrhythmic drugs, pulmonary hypertension treatment

493antibiotics

interaction with host defences 374–6new agents 385–91

antisense antinucleotides 390–1chemical modification of known agents 387–9inhibitors of new targets 389–90novel classic antimicrobial agents 385–7potentiators of known antibiotics 389

pharmacokinetics 372–4resistance patterns 368–71, 389see also specific drugs

antibodies see immunoglobulinsanticholinergic bronchodilators 105–15

clinical efficacy 109–14acute exacerbations of COPD 112acute severe asthma 110

against specific stimuli 109children 110–11combination therapy 114dose–response 109sleep quality 112stable asthma 109–10stable COPD 111–12

pharmacokinetics 108–9pharmacology 107–9rationale for use 105–7side effects 114–15see also specific drugs

anticoagulation therapy 462pulmonary hypertension 492

antihistamines 121antitussive therapy 567–8, 570–1

antileukotriene drugs 125asthma treatment 130–2

efficacy 129–30with corticosteroids 42

cystic fibrosis treatment 433–4safety of 130see also leukotrienes; specific drugs

antimalarial drugs, sarcoidosis treatment 285see also specific drugs

antimicrobials see antibioticsantioxidants

cystic fibrosis treatment 431fibrotic lung disease treatment 350–1

antiphospholipid antibody (aPLa) syndrome 460, 469antiproteases, cystic fibrosis treatment 430–1antisense antinucleotides 390–1antitussive therapy 565–75

ACE inhibitor-induced cough 572asthma and 568–9baclofen 574benzonatate 574bronchiectasis 572–3caramiphen 573–4chronic bronchitis 572–3diphenhydramine 573gastroesophageal reflux disease 569–70levodropropizine 574opioids 561, 573postinfectious cough 571postnasal drip syndrome 567–8potassium channel openers 179site and mechanisms of action 560–2see also cough

apoptosiscorticosteroid effects 36

580 Index






fibrotic lung disease treatment 348–9aprikalim 175arachidonic acid 124, 432arterial oxygen tension, �2-agonist effects 86aspirin 232aspirin-induced asthma 128, 131asthma 3, 22, 140–1

antiallergic drug treatment 119–22chromones 119–21histamine H1-receptor antagonists 121ketotifen 121–2

anticholinergic bronchodilator treatment 109–11acute severe asthma 110children 110–11sleep quality and 112stable asthma 109–10

antileukotriene drug treatment 130–2efficacy 129–30

aspirin-induced asthma 128, 131�2-agonist treatment 56

airway hyperresponsiveness 74bronchospasm 72–3chronic therapy 76–84late asthmatic response 73–4mortality increase 84–6nocturnal asthma 74–5

bradykinin and 190–1corticosteroid treatment 32–50

acute severe asthma 48–9airway hyperresponsiveness 38children 39–40clinical efficacy 39–41dose-response studies 40inflammation control 38inhaled corticosteroids 39–48pharmacokinetics 43–4systemic corticosteroids 48–9with additional bronchodilators 42

corticosteroid-resistant asthma 49mechanisms of resistance 49–50

corticosteroid-sparing therapy 42–3cough and 568–9forms of 3inflammation 4–5, 6–8, 126, 140–1leukotriene importance 125–9

airway hyperresponsiveness 126airway inflammation 126airway obstruction 125–6allergen-induced asthma 128–9exercise and cold-induced bronchoconstriction

126–8, 132

lumenal secretions 5–6airway plugging 6bronchoalveolar lavage 6sputum 5–6

nocturnal�2-agonist treatment 74–5potassium channel openers and 177

phosphodiesterase activity 142phosphodiesterase inhibitor treatment 137–8, 155–6remodelling 4–5, 141

airway wall nerves 22airway wall thickening 4bronchial smooth muscle 17, 19connective tissue 17mucus-secreting elements 19reticular basement membrane 14–15surface epithelium 13–14

rhuMAb-E25 treatment 208–9similarity with COPD 9–10

atopic dermatitis 141–2atrial natriuretic peptide (ANP) 509–10atrial septostomy 495–7atropine 105, 107

dose–response 109pharmacokinetics 108–9side effects 114

atropine methonitrate 107, 109, 115atypical adenomatous hyperplasia (AAH) 520autoimmune thryroiditis 469autologous bone marrow transplantation (ABMT),

pulmonary toxicity 269azathioprine (AZA)

asthma treatment 42collagen vascular disease treatment 265, 267cryptogenic fibrosing alveolitis treatment 254–5sarcoidosis treatment 284

azelastine 122azithromycin

chronic bronchial suppuration treatment 415, 420, 423pneumonia treatment 378, 379

aztreonam 415

B-lymphocytesgene rearrangement 196phosphodiesterase inhibitor effects 150–1

baclofen, antitussive therapy 574Bacteroides 365bagassosis 286basophils

asthma and 8phosphodiesterase inhibitor effects 146–7

Index 581






BAY-1005asthma treatment 129

BDPasthma treatment 41, 43side effects 45, 46, 47

beclomethasone 202Behcet’s syndrome 298, 299bemoradan 147benzafentrine 147, 155benzonatate, antitussive therapy 574benzopyrans 175benzothiadiazines 175beraprost 491�2-adrenoceptors

�2-agonist effects 61–2corticosteroid effects 34–5polymorphisms 62

�2-agonists 56, 201administration route 62–3adverse effects 86asthma deaths and 84–6

case control studies 84–5mechanisms 85–6

asthma treatment 56airway hyperresponsiveness 74bronchospasm 72–3late asthmatic response 73–4nocturnal asthma 74–5with corticosteroids 42

chronic therapy 76–84bronchial hyperresponsiveness 79–80bronchodilator tolerance 76–7loss in bronchoprotection 77–9regular vs. symptomatic therapy 80–4

clinical effects of 72–6COPD treatment 56, 75–6duration of action 63–4

baseline FEV 63bronchospasm 63–4

efficacy 65–6mechanism of action 59–62pulmonary hypertension treatment 493selectivity 64–5sites of action 66–72

airway smooth muscle 66epithelial cells 68–9inflammatory cells 69–72mast cells 66–8

structure and metabolism 56–9see also specific drugs

�-lactams 375

allergic reactions 440chronic bronchial suppuration treatment 414–15, 418,

421pneumonia treatment 379, 380, 383–4resistance 370, 371, 389see also specific drugs

betamethasone, asthma treatment 48bimakalim 175, 176, 177, 178biopsy 248–9bird breeder’s lung 286, 289bleomycin, pulmonary toxicity 268BO-2727 387bone metabolism, corticosteroid effects 46bone morphogenetic protein receptor II (BMPR2) 469–70Bosentan, fibrotic lung disease treatment 351bradykinin 185

asthma and 190–1brain metastases, lung cancer and 543

prophylactic cranial irradiation 544–5BRL-42715 389BRL-55834 175, 178bronchial epithelium see epitheliumbronchial hyperresponsiveness see airway

hyperresponsiveness (AHR)bronchial smooth muscle

asthma 17, 19�2-agonist effects 66COPD 17–19dedifferentiation 19phosphodiesterase inhibitor effects 154–5potassium channel openers 176

bronchiectasis 403–4airway vessel remodelling 20bacteriology 407–8clinical features 408–9cough and 572–3investigations 409–12pathophysiology 404–7smoking and 404

bronchiolitischronic 10constrictive 293diffuse panbronchiolitis (DPB) 298follicular 273in COPD 3, 10obliterative (OB) 293–8occupational 268

bronchiolitis obliterans organizing pneumonia (BOOP)249, 291

bronchiolitis obliterans with interstitial pneumonia (BIP)249

582 Index






bronchitischronic 9

cough and 572–3follicular 273in COPD 3, 9industrial 268

bronchoalveolar lavage (BAL) 249asthma 6

bronchospasm, �2-agonist effects 63–4, 72–3bronchus associated lymphoid tissue (BALT) 273

hyperplasia 273BSW17 206budesonide

asthma treatment 39–43children 40pharmacokinetics 43

side effects 45, 46Burkholderia cepacia 371

chronic bronchial suppuration 407cystic fibrosis 434, 440–1, 442–3

busulfan, pulmonary toxicity 268

C-fibre receptors 553, 561C-fibres 554, 555–7, 561c-myb proto-oncogene 509cabergoline, pulmonary toxicity 269calcitonin gene-related peptide (CGRP) 184calcium channel blockers

adverse effects 487chronic hypoxic lung disease and 494connective tissue disease treatment 494pulmonary hypertension investigation 482–3pulmonary hypertension treatment 485–7

primary pulmonary hypertension 485–6secondary pulmonary hypertension 486–7

candidiasis, oropharyngeal, corticosteroid effects 44capsaicin 186–7captopril, fibrotic lung disease treatment 348caramiphen, antitussive therapy 573–4carbacephalosporins 387carbapenems 387, 414–15carbenicillin 437, 439Carboplatin, small cell lung cancer treatment 539,

544carcinoma in situ (CIS) 519, 523–5

see also lung cancercardiac glycosides, pulmonary hypertension treatment

492–3cardiopulmonary exercise tests (CPET) 247carmustine (BCNU), pulmonary toxicity 268cataracts, corticosteroids and 47

catechol-O-methyl transferase (COMT) 56, 58CcdB 390CD4 cells 12

asthma 6, 8�2-agonist effects 71

CD8 cells 12�2-agonist effects 71bronchiolitis 10COPD 8–9, 10, 12

CD23 201, 204–5CD40 198–9CDK2 kinase 510CDKN2 gene mutations 521, 522, 524CDP840 145, 155cefaclor 375cefadroxil 202cefetamet 375cefodizime 375cefotaxime 379cefoxitin 442ceftazidime 375, 437, 439, 440ceftriaxone 375, 420cefuroxime 379cell signalling 218–37

extracellular regulated kinase (ERK) pathway 223–6IkB kinase (IKK) pathway 229–32Jun-N-terminal kinase (JNK) pathway 226–9p38 kinase pathway 218–23protein kinase C (PKC) 232–5

CEP-1347 (Cephalon) 228–9cephalexin 435–6cephalosporins 375

chemical modifications 387chronic bronchial suppuration treatment 414, 420pneumonia treatment 377–8, 379, 384resistance 371see also specific drugs

CGP51901/Hu-901 206Charcot–Leyden crystals 6chemotherapy

side effects 539small cell lung cancer 535, 548–3

alternating chemotherapy regimens 540CNS metastases 543dose intensification 540–1elderly patients 542–3new drugs 545–6patients with poor performance status 542–3relapsed patients 542weekly chemotherapy 541–2

chest radiography 247

Index 583






childrenasthma, corticosteroid treatment 39–40pulmonary hypertension 497–8

congenital heart defects 498persistent pulmonary hypertension of the newborn

(PPHN) 498, 512–13primary pulmonary hypertension 498

Chlamydia pneumoniaecough and 571pneumonia 364–5, 366, 380–1

chloramphenicolchronic bronchial suppuration treatment 417resistance 370

chlorine 268chloroquine, sarcoidosis treatment 285chromatin structure, corticosteroid effects 33chromones 119–21

asthma treatment 119–21chronic bronchial suppuration 403

antibiotic treatment 414–24aminoglycosides 417�-lactams 414–15chloramphenicol 417future developments 424intravenous antibiotics 420–2macrolides 415–16, 423oral antibiotics 420principles 418–20prophylaxis 422–3quinolones 416tetracyclines 416–17trimethoprim-sulfamethoxazole 417

bacteriology 407–8clinical features 408–9investigations 409–12non-antibiotic treatment 412–14

airway inflammation 412–13hypogammaglobulinemia 413physiotherapy 412respiratory failure 413surgical treatment 413–14

pathophysiology 404–7chronic eosinophilic pneumonia (CEP) 289–90chronic hypoxic lung disease 494chronic obstructive pulmonary disease (COPD) 3, 23,

140–1, 504anticholinergic bronchodilator treatment 111–12

acute exacerbations 112sleep quality and 112stable COPD 111–12, 115

�2-agonist treatment 56, 75–6

corticosteroid treatment 50–1, 572emphysema and 3, 10, 21–2inflammation 4–5, 8–13, 50

CD8� cell 12macrophage 11–12neutrophil 10–11vascular inflammation 12–13

phosphodiesterase inhibitor treatment 137, 155–6remodelling 4–5, 141

airway wall thickening 4bronchial smooth muscle 17–19connective tissue 17mucus-secreting elements 19reticular basement membrane 15–17

similarity with asthma 9–10smoking and 3, 8–9

Churg–Strauss syndrome (CSS) 299, 304antileukotrienes and 130

cigarette smoking see smokingcilastatin 415cilomilast 145, 147, 156cilostamide 147cilostazol 147, 154

asthma treatment 155cinalukast, asthma treatment 127ciprofloxacin 375, 416, 420

cystic fibrosis management 436–7, 438–9resistance 370, 437

Cisplatin, small cell lung cancer treatment 539, 544Cl-930 149clarithromycin 376, 423

pneumonia treatment 378–9, 380clerocidin 390clinafloxacin 388clindamycin, pneumonia treatment 384co-amoxiclav

cystic fibrosis management 436pneumonia treatment 379

coagulation abnormalities 457–9codeine, antitussive therapy 561, 562, 573colchicine

amyloidosis treatment 317cryptogenic fibrosing alveolitis treatment 255

cold air-induced bronchoconstriction 126–7colistin 422, 437, 438–9

intravenous 440collagen 17collagen vascular diseases 261–7

dermatomyositis (DM) 264–5mixed connective tissue disease (MCTD) 266overlap syndrome 266

584 Index






polymyositis (PM) 264–5progressive systemic sclerosis (PSSc) 262–4rheumatoid arthritis (RA) 264Sjogren’s syndrome (SS) 266–7systemic lupus erythematosus (SLE) 265–6

collagenases 343congenital heart disease 494, 498connective tissue, corticosteroid effects 46–7connective tissue diseases 494corticosteroid treatment 32–51

acute eosinophilic pneumonia 290–1asthma 32–50

acute severe asthma 48–9airway hyperresponsiveness reduction 38children 39–40clinical efficacy 39–41dose-response studies 40inflammation control 38inhaled corticosteroids 39–48pharmacokinetics 43–4systemic corticosteroids 48–9with additional bronchodilators 42

chronic eosinophilic pneumonia 289–90Churg–Strauss syndrome 304collagen vascular diseases 262

dermatomyositis 265polymyositis 265progressive systemic sclerosis 263–4rheumatoid arthritis 264Sjogren’s syndrome 267

COPD 50–1, 572inhaled corticosteroids 50–1systemic corticosteroids 51

cough 571cryptogenic organizing pneumonia 292–3cystic fibrosis 430drug-induced lung disease 269glucocorticoid receptors 32hypersensitivity pneumonia 289idiopathic interstitial pneumonia

acute interstitial pneumonia 259cryptogenic fibrosing alveolitis 253–4desquamative interstitial pneumonia (DIP) 257

IgE and 202molecular mechanisms 32–8

effects on cell function 36–8effects on chromatin structure 33effects on gene transcription 32–3, 35inflammation suppression 34–6, 50transcription factor interactions 33

relapsing polychondritis 315

resistance mechanisms 49–50sarcoidosis 282–4side effects 44–8, 51

bone metabolism 46central nervous system 47–8connective tissue 46–7delivery system effects 45dysphonia 44growth retardation 47hematological effects 47hypothalamic–pituitary–adrenal axis 45–6inhaled corticosteroids 44–8metabolic effects 47ocular effects 47oropharyngeal candidiasis 44pregnancy and 48

Wegener’s granulomatosis 301–3see also specific drugs

corticotrophin (ACTH), corticosteroid effects 45cortisol, corticosteroid effects 45–6cough 553–63

ACE inhibitors and 189–90, 557, 560, 571–2asthma and 568–9bronchiectasis and 572–3chronic bronchitis and 572–3gastroesophageal reflux disease (GERD) and 569–71kinin role 189–90mechanisms 559–60

anatomical site for cough reflex initiation 557central nervous mechanisms 557–9

postinfectious cough 571postnasal drip syndrome (PNDS) 567–8protussive therapy 574–5sensory physiology 554–7

C-fibre endings 555rapidly adapting stretch receptors (RARs) 554–5relative roles of airway sensory receptors 555–7slowly adapting stretch receptors (SARs) 554

tachykinin role 190, 556–7treatment see antitussive therapy

CP6679 387CP80633 152CP96345 188, 189CP99994 189, 190CREB binding protein (CBP) 33Creola bodies 5–6CREST syndrome 486cromakalim 172, 174, 176–7

airway hyperresponsiveness and 177–8bronchodilation and 177cough and 179

Index 585






cromoglycate, IgE and 202cromolyn sodium 119

asthma treatment 120mechanisms of action 119–20

cryptogenic fibrosing alveolitis (CFA) 249–56clinical features 251–2prevalence 250treatment 253–6see also idiopathic pulmonary fibrosis (IPF)

cryptogenic organizing pneumonia (COP) 249, 291–3CSAIDs (cytokine-suppressive anti-inflammatory drugs)

221, 222Curshmann’s spirals 5, 19cyanoguanidines 175cyclic AMP

allergy and 141–2phosphodiesterase inhibitor effects 147–53

cyclophosphamide (CP)collagen vascular disease treatment 263–4, 265cryptogenic fibrosing alveolitis treatment 254–5pulmonary toxicity 268sarcoidosis treatment 284–5side effects 302–3Wegener’s granulomatosis treatment 301–2

cyclosporin Aasthma treatment 42, 202collagen vascular disease treatment 265cryptogenic fibrosing alveolitis treatment 255IgE and 202sarcoidosis treatment 285

cysteinyl leukotriene receptor Type 1 (CysLT) 125cysteinyl leukotrienes 124–5, 126, 128–9

see also leukotrienescystic fibrosis (CF) 428–43

anti-inflammatory drug treatment 430–4antioxidants 431antiproteases 430–1corticosteroids 430deoxyribonuclease 433fatty acid supplementation 433–4heparin 432interleukin-10 431leukotriene receptor antagonists 433–4macrolides 432NSAIDs 430pentoxifylline 432

infection treatment 434–43antistaphylococcal prophylaxis 435–6B. cepacia 440–1H. influenzae infection 436MRSA 441

new antimicrobials 442–3non-tuberculous mycobacteria 441–2P. aeruginosa infection 436–40Stenotrophomonas maltophilia 441

vaccines against P. aeruginosa 442cystic fibrosis transmembrane conductance regulator

(CFTR) 428, 429, 431cytokine receptor modulation 200–1cytokines

asthma and 7–8�2-agonist effects 67, 71corticosteroid effects 35corticosteroid resistance and 49phosphodiesterase inhibitor effects 149–50pneumonia immunotherapy 391–2pulmonary vascular disease and 463see also specific cytokines

cytomegalovirus 364

D22888 155dalfopristin 385–6dapsone

asthma treatment 42relapsing polychondritis treatment 315–16

delayed pulmonary toxicity syndrome 269denbufylline 147, 155dendritic cells, corticosteroid effects 37deoxyribonuclease (DNase), cystic fibrosis treatment 433dermatomyositis (DM) 264–5desquamative interstitial pneumonia (DIP) 249, 256–7,

336, 341–2dextran 443dextromethorphan, antitussive therapy 573diacylglycerol (DAG) 232, 233diazoxide 175diffuse alveolar damage (DAD) 258, 259diffuse alveolar hemorrhage (DAH) 298

systemic lupus erythematosus 265Wegener’s granulomatosis 300–1

diffuse panbronchiolitis (DPB) 298, 432digoxin, pulmonary hypertension treatment 492–3diltiazem

adverse effects 487primary pulmonary hypertension treatment 485–6pulmonary hypertension investigation 482–3

diperamycin 387diphenhydramine, antitussive therapy 573diuretics, pulmonary hypertension treatment 493docosahexaenoic acid (DHA), cystic fibrosis and 432, 433dorsal respiratory group (DRG) 559Doxoribicin, small cell lung cancer treatment 544

586 Index






doxycillin 379, 416, 420drug-induced pneumonitis/fibrosis 268–70dysphonia, corticosteroid effects 44dysplasia 519

E-selectin 36edema, �2-agonist effects 68–9eicosanoids 124

fibrotic lung disease treatment 347eicosatrienoic acid (ETA), cystic fibrosis and 432Eisenmenger’s syndrome 494emphysema 20–2

centriacinar 20in COPD 3, 10, 21–2panacinar 20

enalapril, fibrotic lung disease treatment 348endothelial cells (ECs)

�2-agonist effects 68–9corticosteroid effects 37phosphodiesterase inhibitor effects 153–4pulmonary vascular disease and 463, 466thrombosis and 457–8

endothelial dysfunction 458pulmonary vascular disease and 455, 464, 466

endothelin-1 35, 351, 455fibrotic lung disease and 351

endothelin antagonistsfibrotic lung disease treatment 351persistent pulmonary hypertension of the newborn

treatment 513endothelium-derived relaxing factor 481

see also nitric oxideendotoxin antagonists 391enprophylline 137, 138, 139, 149, 152Enterobacter 367, 368, 382

drug resistance 371eosinophils

asthma 6–8, 9�2-agonist effects 69–71bronchitis 9COPD 9–10corticosteroid effects 36–7, 47eosinophilic pneumonia 289–91

acute 290–1chronic 289–90

phosphodiesterase inhibitor effects 147–8eperezolid 386epithelium

corticosteroid effects 37hyperplasia 519phosphodiesterase inhibitor effects 152–3

remodelling in asthma 13–14smoking damaged bronchial epithelium 528–9

epoprostenol 461erythromycin 376

chronic bronchial suppuration treatment 415, 423cystic fibrosis treatment 432pneumonia treatment 378–9, 380resistance 369, 370

Escherichia coli 367, 407Etoposide, small cell lung cancer treatment 539, 542, 544evernonomycins 386exercise-induced bronchoconstriction 126–8, 132extracellular regulated kinases (ERK) 223

signalling pathway 223–6extracorporeal membrane oxygenation (ECMO) 512

factor V Leiden deficiency 459–60Farmer’s Lung disease (FLD) 286, 288fatty acid supplementation, cystic fibrosis and 432–3felodipine, secondary pulmonary hypertension treatment

487fenoterol 56, 61, 62, 201

asthma deaths and 84–5chronic therapy

bronchial hyperresponsiveness and 80regular vs. symptomatic therapy 81

combination therapy 114duration of action 63efficacy 65, 66inflammatory cells and 69, 72selectivity 64–5structure and metabolism 59

FHIT gene 523fibrinogen 458fibrinopeptide A (FP-A) 458fibroblastic foci 250, 342fibrosing alveolitis (FA) 261–2

dermatomyositis 264–5mixed connective tissue disease 266polymyositis 264–5progressive systemic sclerosis 262–4rheumatoid arthritis 264Sjogren’s syndrome 266–7systemic lupus erythematosus 266see also cryptogenic fibrosing alveolitis

fibrosis 336, 341COPD 17drug-induced 268emphysema 21–2Gaucher’s disease (GD) 271Hermansky–Pudlak syndrome 270

Index 587






fibrosis (cont.)neurofibromatosis 270–1Niemann–Pick disease 271non-specific interstitial 259–61progressive pulmonary 261subepithelial 15see also cystic fibrosis; idiopathic pulmonary fibrosis

filgastrim 392fish oil supplementation, cystic fibrosis 432–3FK-224 189, 190FK-888 190flucloxacillin 435flunisolide, asthma treatment 41, 43fluoroquinolones 388

chemical modifications 388chronic bronchial suppuration treatment 416pneumonia treatment 379, 380resistance 371

fluticasone propionate (FP)asthma treatment 39, 41, 43side effects 45

follicular bronchitis/bronchiolitis (FB) 273formoterol 56, 61

administration route 62, 63asthma treatment

airway hyperresponsiveness 74bronchospasm 73late asthmatic response 73–4nocturnal asthma 75with corticosteroids 42

chronic therapyairway hyperresponsiveness 80bronchodilator tolerance 76–7loss in bronchoprotection 78, 79regular vs. symptomatic therapy 83–4

COPD treatment 75duration of action 63, 64efficacy 66selectivity 65sites of action

airway smooth muscle 66endothelial cells 68inflammatory cells 69, 70, 71, 72mast cells 66–8

structure and metabolism 59forskolin 149, 153FR-133605 222FR-167653 222–3FR-173657 189fractures, corticosteroid effects 46Fusobacterium 365

G-proteins 59, 61gastroesophageal reflux disease (GERD) 569–71gatifloxacin 388, 416Gaucher’s disease (GD) 271gemifloxacin 388gene therapy, pulmonary vascular disease 510–11gentamicin 422, 437giant cell interstitial pneumonia (GIP) 249glaucoma, corticosteroids and 47glomerulonephritis

pauci-immune 298, 299, 301rapidly progressive (RPGN) 300

glucocorticoid receptors (GRs) 32–3glucocorticoid response elements (GREs) 33glucocorticosteroids see corticosteroid treatmentglutathione, fibrotic lung disease and 350–1

cystic fibrosis 431glycopyrrolate bromide 107, 109, 115glycylcyclines 387goblet cell hyperplasia 19gold, oral

asthma treatment 42pulmonary toxicity 269

graft-vs.-host disease (GVHD) 293granulocyte–macrophage colony stimulating factor

(GM–CSF)asthma and 8pulmonary alveolar proteinosis and 313

grepafloxacin, pneumonia treatment 379, 380growth, corticosteroid effects 47

Haemophilus influenzaechronic bronchial suppuration 407, 418cough and 567cystic fibrosis 434, 436drug resistance 370pneumonia 364–7, 377, 386

Haemophilus parainfluenzae 407Hamman-rich syndrome 258–9Henoch–Schonlein purpura 298heparin, cystic fibrosis treatment 432HER-2/NEU gene family 520Hermansky–Pudlak syndrome (HPS) 270high molecular weight-kininogen (HMWK) 185high resolution computed tomography (HRCT) 247–8histamine 121

�2-agonist effects 66, 67phosphodiesterase inhibitor effects 147

histamine receptor antagonists 121gastroesophageal reflux disease-induced cough

treatment 570–1

588 Index






histone acetylation 33HOE-140 189, 191HOE-234 176hospital-acquired pneumonia (HAP) see pneumoniahu-901 209–10huG-CSF, pneumonia treatment 392huMAb-E25 207–9human immunodeficiency virus (HIV) infection 495human peripheral blood mixed mononuclear cells

(HPBMC) 139–40humidifier lung 286hydrocortisone, asthma treatment 48–9hydroxy-methylglutaryl coenzyme A (HMG-CoA),

pulmonary toxicity 269hydroxychloroquine

asthma treatment 42sarcoidosis treatment 285

hyper-IgE syndrome 202hypersensitivity pneumonia 269, 286–9

treatment 288–9hypocalciuric hypercalcemia and interstitial lung disease

271hypogammaglobulinemia treatment 413hypokalemia, �2-agonists and 86hypothalamic–pituitary–adrenal axis, corticosteroid

effects 45–6

iberiotoxin 176, 177IBMX 146–55ibudilast 122, 155ibuprofen, cystic fibrosis treatment 430ICAM-1 36idiopathic interstitial pneumonias 249

see also specific typesidiopathic pulmonary fibrosis (IPF) 249–56

clinical features 251–2mortality 336new drugs theoretically of value 343–8

eicosanoids 347interferon-beta 345interferon-gamma 345–7pirfenidone 343–5relaxin 347–8

pathogenesis 252–3, 340–3treatment 253–6

ACE inhibitors 348antioxidants 350–1apoptotic agents 348–9endothelin receptor antagonists 351interleukin-10 352keratinocyte growth factor (KGF) 349–50

suramin 349treatment evaluation problems

demonstrating benefit 336–7diagnostic contamination 338–9end-point selection 339–40selection bias 337–8

see also cryptogenic fibrosing alveolitis (CFA)Ifosphamide 542IgE 195

anti-IgE therapeutic antibodies 205–11safety issues 210–11

drugs affecting synthesis 201–5drugs in clinical use 201–2new/investigational drugs 203–5

synthesis regulation 195–201B cell gene rearrangement 196cytokine/cytokine receptor modulation 200–1signals required for production 196–9

IkB kinase (IKK) 230signalling pathway 229–32

iloprost 491imazodan 147imipenem 415, 442immunoglobulins 195–6

class switching 196heavy chain gene rearrangement 196, 197see also IgE

inflammationasthma 4–5, 6–8, 140–1

leukotrienes and 126�2-agonist effects 69–72chronic bronchial suppuration 412–13, 423–4chronic bronchitis/bronchiolitis 9–10COPD 4–5, 8–13, 50

vascular inflammation 12–13corticosteroid suppression of 34–6, 50cystic fibrosis 429emphysema 10, 21fibrosis and 341–2inhibitors of 508–9kinin role 187–8neurogenic inflammation 185–6

modulation of 186–7NF-KB role 229phosphodiesterase inhibitor effects 146–55smoking and 8–12, 21tachykinin role 187–8theophylline effects 138–40treatment 412–13

influenza virus 364interferon-beta, fibrotic lung disease treatment 255, 345

Index 589






interferon-gammafibrotic lung disease treatment 255, 345–7phosphodiesterase inhibitor effects 150pneumonia treatment 391

interleukins (IL)asthma 7–8chronic bronchitis 10corticosteroid resistance and 49IgE synthesis and 196, 199, 200inhibition of 200interleukin-10 (IL-10)

cystic fibrosis treatment 431fibrotic lung disease treatment 352

phosphodiesterase inhibitor effects 149–50interstitial lung diseases (ILDs) 247, 249, 504

diagnosis 247–9drug-induced 268–70hypocalciuric hypercalcemia and 271occupational 268treatment 249see also specific diseases

ipratropium 107, 115asthma treatment 109–10

children 110–11combination therapy 114COPD treatment 111–12dose–response 109pharmacokinetics 109side effects 114–15sleep quality and 112

Irinotecan, small cell lung cancer treatment 546isocyanates 268isoetharine 63isoprenaline 57–8, 61

administration route 62asthma deaths and 84, 85duration of action 63efficacy 65inflammatory cells and 69, 71, 72selectivity 64

isoproterenol, primary pulmonary hypertensiontreatment 493

Janus family kinases 199Jun N-terminal kinases (JNK) 226

signalling pathway 226–9

K252a 234K channels see potassium channelskallidin 185kallikreins 185

keratinocyte growth factor (KGF), fibrotic lung diseasetreatment 349–50

ketolides 386ketotifen

asthma treatment 121–2mechanisms of action 121

kinin receptors 185antagonists 186, 188–9

kinins 185role in cough 189–90role in inflammation 187–8

Klebsiella 367, 382pneumoniae 365drug resistance 371

L-167307 222L-783277 226Langerhans’ cell histiocytosis (LCH) 304large cell carcinoma 519leflunomide 204Legionella 367, 384

pneumonia 365, 366, 386Legionnaires’ disease 367lemakalim 176, 177leukotrienes 433

cysteinyl leukotrienes 124–5, 126, 128–9importance in asthma 125–9

airway hyperresponsiveness 126airway inflammation 126airway obstruction 125–6allergen-induced asthma 128–9aspirin-induced asthma 128, 131cold air-induced bronchoconstriction 126–7exercise-induced bronchoconstriction 126–8, 132

inhibition of 125in fibrotic lung disease 347

synthetic pathways 124–5see also antileukotriene drugs

levcromakalim 175, 178, 179levodropropizine, antitussive therapy 574levofloxacin 375, 416

pneumonia treatment 379, 380linezolid 386linoleic acid, cystic fibrosis and 432lipid A 389–90, 391lipocortin-1 34lipopolysaccharide (LPS) 389–90, 3915-lipoxygenase 125lomefloxacin resistance 370loratadine 567losartan 572

590 Index






lovastatin, fibrotic lung disease treatment 348–9low molecular weight-kininogen (LMWK) 185LP-805 175lung biopsy 248–9lung cancer 519

development of 519–20, 522–5molecular abnormalities 520–30

accumulation of genetic changes 525dominant oncogenes 520–1genomic instability 527multistage development of lung cancer 522–3precursor lesions 526–7recessive oncogenes 521sequential genetic changes 523–5sizes of patches with genetic changes 529telomerase dysregulation 527–8tumour type-specific genetic changes 521–2

molecular markers for early detection 528precursor lesions 526–7

genetic changes 526–7see also non-small cell lung carcinoma (NSCLC); small

cell lung carcinoma (SCLC)lung transplantation 249

chronic bronchial suppuration 413–14contraindications to 249cryptogenic fibrosing alveolitis 255–6obliterative bronchiolitis 295–8pulmonary hypertension 495sarcoidosis 285–6

LY-171883, asthma treatment 129–30LY-333328 388LY-333531 234, 235lymphangioleiomyomatosis (LAM) 308–11lymphocytes

asthma and 6–7�2-agonist effects 71–2see also T-lymphocytes

lymphoid interstitial pneumonia (LIP) 249, 272lymphoma, primary pulmonary 273–4lymphomatoid granulomatosis (LYG) 274lymphoproliferative disorders 271–2

post-transplant 275see also specific disorders

M39 222M50367 203–4MAb MAE11/E25 205–6, 207–9macrolides 376

chronic bronchial suppuration treatment 415–16, 423cystic fibrosis treatment 432, 442pneumonia treatment 378–9, 380–1

resistance 369, 370see also specific drugs

macrophagesasthma and 8�2-agonist effects 71COPD and 11–12corticosteroid effects 36idiopathic pulmonary fibrosis and 341phosphodiesterase inhibitor effects 152smoking and 10, 12

MAE11/E25 205–6, 207–9mast cells

asthma and 8�2-agonist effects 66–8corticosteroid effects 37phosphodiesterase inhibitor effects 146–7

matrix metalloproteinases (MMPs)COPD and 11–12inhibitors of 508

MEN1 gene 530meropenem 415metalloproteinases see matrix metalloproteinases (MMPs)methicillin resistance 367, 368, 369, 384methotrexate

asthma treatment 42collagen vascular disease treatment 265pulmonary toxicity 269sarcoidosis treatment 284Wegener’s granulomatosis treatment 303

methylprednisoloneacute interstitial pneumonia treatment 259COPD treatment 51Wegener’s granulomatosis treatment 301

methylxanthines 141, 148–9mevalonic acid, fibrotic lung disease and 348–9mezlocillin 440microcin B17 390microsatellite alterations (MAs) 427microscopic polyangiitis (MPA) 298, 299, 303midostaurin 234–5migis antibodies 206–7milrinone 147, 153, 154minocycline 416minoxidil 175mitogen activated protein kinase activated protein

kinase-2 (MAPKAP kinase-2) 220mitogen activated protein kinases (MAPKs) 218, 223mitomycin, pulmonary toxicity 268mixed connective tissue disease (MCTD) 266MK-571 126, 129MK-591 129

Index 591






MK-886 129MKS492 155monocytes, phosphodiesterase inhibitor effects 151–2montelukast 125

asthma treatment 126, 128, 131efficacy 130

side effects 130Moraxella catarhalis

chronic bronchial suppuration 407, 418drug resistance 370–1pneumonia 364, 365, 386

morphine, antitussive therapy 561, 573motapizone 152–5moxifloxacin 388, 416mucus

asthma 5, 19COPD 19secretion

corticosteroid effects 38potassium channel openers and 179

see also chronic bronchial suppurationmuscarinic receptor subtypes 106–7mushroom worker’s lung 286MYC gene family 520–1, 522Mycobacterium avium-intracellulare 407–8Mycoplasma pneumoniae

cough and 571pneumonia 364–5, 366, 386

myocyte-enhancer factor 2 (MEF2) 220

N-acetylcysteine 350–1nedocromil, IgE and 202nedocromil sodium 120

asthma treatment 121mechanisms of action 120–1

neonatal pulmonary hypertension 511–13neurofibromatosis (NF) 270–1neurogenic inflammation 185–6

modulation of 186–7neurokinins (NK)

antagonists 561neurokinin A (NKA) 184, 556neurokinin B (NKB) 184receptors 35–6, 189, 190see also tachykinins

neutrophilsasthma 7�2-agonist effects 72chronic bronchial suppuration 405chronic bronchitis 9COPD 10–11

corticosteroid effects 37phosphodiesterase inhibitor effects 147smoking and 10, 11

nicardipine, pulmonary hypertension treatment 485nicorandil 175Niemann–Pick disease 271nifedipine

adverse effects 487chronic hypoxic lung disease and 494primary pulmonary hypertension treatment 485–6pulmonary hypertension investigation 482–3

nitric oxide (NO) 455, 457, 464, 510persistent pulmonary hypertension of the newborn

treatment 498, 512–13pulmonary hypertension investigation 481

nitric oxide synthase (NOS) 35, 464–5corticosteroid effects 35

nitrofurantoin, drug-induced 270nitrogen dioxide 268nitroquazone 147nodular lymphoid hyperplasia 273non-cardiac pulmonary edema (NPE) 270non-small cell lung carcinoma (NSCLC) 519

tumour type-specific genetic changes 521–2see also lung cancer

non-specific interstitial pneumonitis/fibrosis (NSIP) 249,259–61, 338–9

non-steroidal anti-inflammatory drugs (NSAIDs), cysticfibrosis treatment 430

nosocomial pneumonia see pneumoniaNS004 175NS1619 175, 177, 179nuclear factor of activated T-cells (NF-AT) 35nuclear factor-B (NF-B) 33, 35, 229nucleus tractus solitarus (NTS) 559

obliterative bronchiolitis (OB) 293–8treatment 295–8

occupational lung disease 267–8, 286ofloxacin resistance 370oncogenes 520–1

dominant 520–1recessive 521

opioids, antitussive therapy 561, 573ORG9935 153–5ORG20421 154, 155oropharyngeal candidiasis, corticosteroid effects 44osteoporosis, corticosteroids and 46overlap polyangiitis syndrome 303overlap syndrome 266oxazolidinones 386, 418

592 Index






oxidative stresscystic fibrosis 431fibrotic lung disease and 350

oximetry 247oxitropium bromide 107, 115oxygen therapy, pulmonary hyperplasia 491ozagrel 122

P1060 175P1075 175PA-1806 442parainfluenza virus 364pauci-immune glomerulonephritis 298, 299PD-98059 225pefloxacin 375pemirolast 122D-penicillamine, progressive systemic sclerosis treatment

263penicillin

chronic bronchial suppuration treatment 414, 420pneumonia treatment 377, 379resistance 369, 370, 380

pentoxifylline 139, 147–9, 151, 153–5cystic fibrosis treatment 432sarcoidosis treatment 285

Peptococcus 365Peptostreptococcus 365persistent pulmonary hypertension of the newborn

(PPHN) 498, 512–13treatment 498, 512–13

phosphodiesterase (PDE) enzymes 136, 137classification of 136in allergic disease 141–2in asthma 142PDE4 142–6

phosphodiesterase (PDE) inhibitorsasthma treatment 155–6COPD treatment 155–6effects on inflammatory cells 146–55

airway smooth muscle 154–5B-lymphocytes 150–1basophils 146–7bronchial epithelium 152–3eosinophils 147–8macrophages 152mast cells 146–7monocytes 151–2neutrophils 147T-lymphocytes 148–50vascular endothelium 153–4vascular smooth muscle 154

IgE and 205PDE4 inhibitors 142–3, 144–6side effects 155see also theophylline

physiotherapy, chronic bronchial suppuration 412pigeon breeder’s lung 286, 289pinacidil 175, 177, 179piperacillin 440pirfenidone 343–4

fibrotic lung disease treatment 343–5piroxicam, cystic fibrosis treatment 430plasminogen activator inhibitor-1 (PAI-1) 458platelet activating factor (PAF) inhibitors 509platelets

�2-agonist effects 69functional abnormalities 460–1

Pneumocystis carinii, pneumonia 365pneumonia

acute interstitial (AIP) 249, 258–9community-acquired (CAP) 363

causal pathogens 363–6treatment 377–82

cryptogenic organizing (COP) 249, 291–3desquamative interstitial (DIP) 249, 256–7, 336, 341–2drug resistance patterns 368–71eosinophilic 289–91

acute 290–1chronic 289–90

hypersensitivity 269, 286–9incidence 363lymphoid interstitial (LIP) 249, 272non-specific interstitial (NSIP) 338–9nosocomial (hospital-acquired) 363

causal pathogens 366–7Legionnaires’ disease 367treatment 382–4ventilator-associated pneumonia (VAP) 367–8, 369

treatment 376–92community-acquired pneumonia 377–82endotoxin antagonists 391future options 384–5immunoadjuvant cytokines 391–2new antimicrobial agents 385–91nosocomial pneumonia 382–4see also antibiotics

usual interstitial (UIP) 249–50, 336, 338–9, 341–2pneumonitis, drug-induced 268–70polyarteritis nodosa (PAN) 299polymyositis (PM) 264–5portopulmonary hypertension 495positron-emission tomography (PET) 248

Index 593






post-transplant lymphoproliferative disorder (PTLD) 275postinfectious cough 571postnasal drip syndrome (PNDS) 567–8potassium channel blockers 173potassium channel openers (KCOs) 172, 173, 174–9

ATP-sensitive potassium channels 175large calcium-activated potassium channel 175–6persistent pulmonary hypertension of the newborn

treatment 513potassium channels in airway nerves 176–7potassium channels on airway smooth muscle 176respiratory disease treatment 176–9

airway hyperresponsiveness and 177–9bronchodilation 177cough and 179mucus secretion and 179

potassium channels 172–3pulmonary vascular disease and 455types of 173

ATP-sensitive 174calcium-activated 173large calcium-activated 174small calcium-activated 173–4

see also potassium channel blockers; potassium channelopeners (KCOs)

pranlukast 125, 129, 131prednisolone

asthma treatment 48, 49COPD treatment 51cryptogenic fibrosing alveolitis treatment 254–5cystic fibrosis treatment 430postinfectious cough treatment 571

prednisoneasthma treatment 48cryptogenic fibrosing alveolitis treatment 253, 254–5IgE and 202sarcoidosis treatment 284Wegener’s granulomatosis treatment 301, 302, 303

pregnancy, corticosteroid safety 48primary pulmonary hypertension (PPH) 453

children 498epidemiology 475genetic contributions 467–70

disease associations 469familial tendency 468genetic studies 469–70

pathogenesis 453pulmonary vascular remodelling 462–7, 506

endothelial cell alterations 466matrix and adventitial changes 467smooth muscle changes 465–6

vessel wall structural changes 463–5pulmonary vascular thrombosis and 456–62

antibodies to fibrin-bound t-PA 461anticoagulation studies 462coagulation abnormalities 457–9inherited thrombophilic states 459–60platelet function abnormalities 460–1

pulmonary vasoconstriction and 454–6treatment

beta-agonists 493calcium channel blockers 485–6lung transplantation 495prostacyclin 488–9

see also pulmonary hypertensionprimary pulmonary lymphoma 273–4progressive systemic sclerosis (PSSc) 262–4, 469Prolastin 431prostacyclin 454–5, 457, 487–8

adverse effects 490connective tissue disease treatment 494pulmonary hypertension investigation 480–1pulmonary hypertension treatment 487–91

delivery methods 490–1persistent pulmonary hypertension of the newborn

513portopulmonary hypertension 495primary pulmonary hypertension 488–9secondary pulmonary hypertension 489–90venous hypertension 494

pulmonary thromboembolic disease and 494prostacyclin synthase, gene therapy and 510–11prostaglandin A1 232prostaglandin PGE2 149, 153

fibrotic lung disease treatment 347protease inhibitors 204–5protein kinases 235

protein kinase C (PKC) 232–5protein kinase p38 218

isoforms 218–20signalling pathway 218–23

see also cell signallingProteus 367, 407protussive therapy 574–5pseudoephedrine 567pseudolymphoma 273Pseudomonas aeruginosa

chronic bronchial suppuration 367, 407, 418–23cystic fibrosis 429, 434, 436–40, 442–3drug resistance 371, 389pneumonia 366, 368, 382, 384, 387vaccines against 442

594 Index






PTMAb0005 206PTMAb0011 206pulmonary alveolar proteinosis (PAP) 311–13

treatment 312–13pulmonary arterial hypertension (PAH) 453

genetic component 467pathogenesis 453–4pulmonary vasoconstriction and 454–6see also pulmonary hypertension; pulmonary vascular

disease (PVD)pulmonary eosinophilic granuloma (EG) 304–8

diagnosis 305–7prognosis 307–8treatment 308

pulmonary function tests (PFTs) 247pulmonary hypertension 475

antiarrhythmic treatment 493anticoagulation therapy 492beta-agonist treatment 493cardiac glycoside treatment 492–3children 497–8

congenital heart defects 498persistent pulmonary hypertension of the newborn

(PPHN) 498, 512–13primary pulmonary hypertension 498

classification 476–7combination therapy 511diuretic treatment 493epidemiology 475–7examination 478genetic component 467history 477–8in COPD 20investigation 478–83

right heart catheterization 479vasodilator studies 480–3

monitoring 497neonatal 511–13pathogenesis 453–4prognosis 497surgical treatment 495–7treatment of the pressure overloaded right ventricle 511treatment of the remodelled lung circulation 507–11

angiogenesis factors 507–8gene therapy 511–12inflammation inhibitors 508–9metalloproteinase inhibitors 508smooth muscle cell growth suppression 509–10

vasodilator treatment 483–92calcium channel blockers 485–7oxygen 491

prostacyclin 487–91venesection 493see also primary pulmonary hypertension (PPH);

pulmonary vascular disease (PVD); secondarypulmonary hypertension (SPH)

pulmonary surfactant protein A (SP-A), fibrotic lungdisease and 349

pulmonary vascular disease (PVD) 453, 504–7chronic hypoxic lung disease 494connective tissue diseases 494future treatments 504–13

combination therapy 511of the pressure overloaded right ventricle 511of the remodelled lung circulation 507–11

genetic contributions 467–70monitoring 497portopulmonary hypertension 495prognosis 497pulmonary vasoconstriction 454–6thrombotic arteriopathy 456–62vascular remodelling 462–7, 504, 506

endothelial cell alterations 466matrix and adventitial changes 467vessel wall smooth muscle changes 465–6vessel wall structural changes 463–5

vascular thrombosis 456–62, 494antibodies to fibrin-bound t-PA 461anticoagulation studies 462coagulation abnormalities 457–9inherited thrombophilic states 459–60platelet function abnormalities 460–1

see also pulmonary hypertensionpulmonary vascular resistance (PVR) 453, 454pyrimidines 175

quercetin 232quinolones

chronic bronchial suppuration treatment 416, 418, 420cystic fibrosis management 436–7resistance 416

quinupristin 385–6

radionuclide scans 248radiotherapy, small cell lung cancer 535, 543–5

prophylactic cranial irradiation 544–5rapidly adapting stretch receptors (RARs) 553, 554–7, 561rapidly progressive glomerulonephritis (RPGN) 300RAS gene mutations 520, 522, 523, 530

as molecular markers for lung cancer 528RB gene mutations 521, 522, 523receptor-activity-modifying proteins (RAMP) 184

Index 595






relapsing polychondritis (RP) 313–16diagnosis 314–15treatment 315–16

relaxin, fibrotic lung disease treatment 347–8remodelling 3, 13–22

airway vessels 19–20, 462–7, 504, 506endothelial cell alterations 466–7structural changes 463–5

airway wall nerves 22asthma and 4–5, 6–8, 141bronchial smooth muscle 17–19, 465–6connective tissue 17COPD and 4–5, 141definition 5emphysema and 20–2extracellular matrix 467mucus-secreting elements 19primary pulmonary hypertension 462–7, 506reticular basement membrane 14–17surface epithelium 13–14

repirinast 122respiratory bronchiolitis interstitial lung disease (RBILD)

249, 257–8respiratory bronchiolitis (RB) 257respiratory failure

cystic fibrosis 428treatment 413

respiratory syncytial virus (RSV) 364reticular basement membrane, remodelling 14–17rheumatoid arthritis (RA) 264rilmakalim 175, 178Ro 07-3149 389Ro 09-2210 226Ro 20-1724 147, 149, 151–3

IgE and 205Ro 31-8425 234, 235Ro 48-1220 389Ro-639141 387Roflumilast 155, 156rolipram 144–5, 146

effects on inflammatory cells 147, 149–55IgE and 205

roxithromycin 376, 423RP-52891 177RP-73401 144, 147, 151, 152, 155rubeola 364RWJ-68354 222

S-4661 387salbutamol 56, 201

administration route 62, 63

asthma deaths and 84–5asthma treatment

airway hyperresponsiveness 74bronchospasm 72–3nocturnal asthma 75

chronic therapyairway hyperresponsiveness 79, 80bronchodilator tolerance 76loss in bronchoprotection 77, 78regular vs. symptomatic therapy 81–2

combination therapy 114duration of action 63efficacy 65, 66IgE and 201–2selectivity 64–5sites of action

endothelial cells 68inflammatory cells 69, 70, 71, 72mast cells 67

structure and metabolism 58salmeterol 56, 61, 201

asthma treatmentairway hyperresponsiveness 74bronchospasm 73late asthmatic response 73–4nocturnal asthma 75with corticosteroids 42

chronic therapyairway hyperresponsiveness 80bronchodilator tolerance 76loss in bronchoprotection 77–8, 79regular vs. symptomatic therapy 82–4

COPD treatment 75–6duration of action 63, 64efficacy 66selectivity 65sites of action

airway smooth muscle 66endothelial cells 68–9inflammatory cells 69, 70, 71, 72mast cells 66–8

structure and metabolism 59sarcoidosis 275–86

diagnosis 276–80prevalence 275prognosis 280–2treatment 282–6

SB-203580 221SB-216385 221SB-218795 189SB-220025 221

596 Index






SB-226882 221SB-239063 221–2SC-102 222scopolamine 105, 107SDZ 217-744 175, 178SDZ PCO-400 175, 178secondary pulmonary hypertension (SPH) 454–6, 458–60,

462, 466treatment 493–4

calcium channel blockers 486–7prostacyclin 489–90

see also pulmonary hypertensionsecretory leukoprotease inhibitor (SLPI) 430, 431serotonin 455, 460–1Serratia marcescens 367signalling pathways see cell signallingSignalsome 230, 231siguazodan 147, 155silo filler’s disease 268sitafloxacin 388Sjogren’s syndrome (SS) 266–7, 272SKF94120 155SKF95654 147, 149SKF104353, asthma treatment 128sleep quality, anticholinergic bronchodilator effects 112Slow Reacting Substance of Anaphylaxis (SRS-A) 124slowly adapting stretch receptors (SARs) 553, 554, 557small cell lung carcinoma (SCLC) 519, 535–47

chemotherapy 535, 538–43alternating chemotherapy regimens 540CNS metastases 543dose intensification 540–1elderly patients 542–3new drugs 545–6patients with poor performance status 542–3relapsed patients 542weekly chemotherapy 541–2

prognostic factors 535, 537–8radiotherapy 535, 543–5

prophylactic cranial irradiation 544–5second primary cancers 546–7serum tumour markers 537staging of 536–7surgical treatment 546tumour type-specific genetic changes 521–2see also lung cancer

smoking 8–9, 10bronchial epithelial damage 528–9bronchiectasis and 404COPD and 3, 8–12inflammatory responses 8–12, 21

pulmonary eosinophilic granuloma and 304, 308respiratory bronchiolitis interstitial lung disease and

257–8smooth muscle see bronchial smooth muscle; vascular

smooth muscleSP600125 229–30sparfloxacin, pneumonia treatment 380spiramycin 376sputum 5–6

see also chronic bronchial suppuration; mucussquamous cell carcinoma 519squamous dysplasia 519squamous metaplasia 519SR-48968 189SR-140333 189Staphylococcus aureus

chronic bronchial suppuration 407cystic fibrosis 429, 434, 441

prophylaxis 435–6drug resistance 369–70

methicillin-resistant S. aureus (MRSA) 367–9, 384,387–8, 441

vancomycin-resistant S. aureus (VRSA) 369–70pneumonia 365, 367, 382, 386

staurosporine 232, 234Stenotrophomonas maltophilia 371

chronic bronchial suppuration 407cystic fibrosis 434, 441

Streptococcus milleri 365Streptococcus pneumoniae

chronic bronchial suppuration 407cough and 567drug resistance 368–9, 380pneumonia 364–7, 377, 386

streptogramins 385–6, 418stress activated protein kinases (SAPK) 226substance P (SP) 184, 556–7sulfasalazine, pulmonary toxicity 269suplatast tosilate 122, 203suramin, fibrotic lung disease treatment 349surfactant lipids, fibrotic lung disease and 349systemic lupus erythematosus (SLE) 265–6

T-lymphocytes 12asthma 6, 7, 8�2-agonist effects 71–2chronic bronchitis 9COPD 8–9corticosteroid effects 37phosphodiesterase inhibitor effects 148–50

tachycardia, �2-agonists and 86

Index 597






tachykinin receptor antagonists 186, 188–91tachykinins 184

receptors 189responses to 185–6role in cough 190, 556–7role in inflammation 187–8

Takayasu’s disease 298, 299taurolidine 442–3tazanolast 122teicoplanin

cystic fibrosis management 441pneumonia treatment 384

telomerase dysregulation, lung cancer and 527–8temafloxacin 416terbutaline 56

administration route 62, 63chronic therapy

bronchial hyperresponsiveness 79–80loss in bronchoprotection 77, 78, 79

duration of action 63efficacy 65, 66nocturnal asthma treatment 75sites of action

endothelial cells 68inflammatory cells 69–70, 71, 72

structure and metabolism 58–9terfenadine 567tetracyclines

chemical modifications 387–8chronic bronchial suppuration treatment 416–17

thalidomide, sarcoidosis treatment 285theophylline 137–40

allergy and 141–2anti-inflammatory effects 138–40, 147, 148, 151–5asthma treatment 137–8

with corticosteroids 42COPD treatment 137mechanisms of action 138–40

thiazoles 389thienamycin, chronic bronchial suppuration treatment

414–15thioformamides 175thromboendarterectomy 497thrombosis see pulmonary vascular diseasethrombotic arteriopathy 456–62thromboxane A2 454, 460tiotropium bromide 107, 108, 115

dose–response 109tissue inhibitors of matrix metalloproteinases (TIMPs) 343tissue plasminogen activator (t-PA) 458

antibodies to fibrin-bound t-PA 461

tobacco smoking see smokingtobramycin 422, 437–40tocainide, pulmonary toxicity 269Topotecan, small cell lung cancer treatment 542, 545–6TP53 gene mutations 521, 522, 523, 530tranilast 122transcription, corticosteroid effects 32–3, 35transcription factors, corticosteroid interaction 33triamcinolone, asthma treatment 41, 48trimethoprim/sulfamethoxazole (T/S)

chronic bronchial suppuration treatment 417Wegener’s granulomatosis treatment 303

troleandomycin, asthma treatment 42–3trovafloxacin, pneumonia treatment 379tumour necrosis factor-� (TNF�)

asthma and 8fibrotic lung disease and 347phosphodiesterase inhibitor effects 150, 152

tumour necrosis factor receptor associated family (TRAF)199

U-0126 225usual interstitial pneumonia (UIP) 249–50, 336, 338–9,

341–2prevalence 250see also cryptogenic fibrosing alveolitis

vaccines, against P. aeruginosa 442vancomycin

cystic fibrosis management 441pneumonia treatment 379–80, 384resistance 369–70, 388

vascular endothelium see endothelial cells; endothelialdysfunction

vascular smooth musclephosphodiesterase inhibitor effects 154pulmonary vascular disease and 463, 465–6

suppression of growth and hypertrophy 509–10vascular thrombosis see pulmonary vascular disease (PVD)vasculitides, ANCA-associated 298–9vasculitis, systemic necrotizing 298VCAM-1 36VEGF, pulmonary vascular disease and 463, 508venesection, pulmonary hypertension and 493ventilator-associated pneumonia (VAP) 367–8, 369viral pneumonia 364Von Willebrand factor (vWF) 457, 459VX-745 223

Wegener’s granulomatosis (WG) 298, 299–303treatment 301–3

598 Index






whole lung lavage 312–13WIN-64338 189wound healing 5

abnormal 342

X-linked hyper IgM syndrome 199

YM-934 178

zafirlukast 125asthma treatment 126, 129

efficacy 130side effects 130

zaprinast 147, 155zardaverine 147, 152–5

asthma treatment 155zileuton 125

asthma treatment 126, 127, 128efficacy 130

side effects 130ziracin 386

Index 599






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