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Hal ini menjadi dasar utama terjadinya penyakit obstruksi paru menahun PPOM. Dikatakan merokok merupakan penyebab utama timbulnya PPOM, termasuk emfisema paru paru, bronkitis kronis, dan asma. Hubungan antara merokok dan kanker paru paru telah diteliti dalam 4 5 dekade terakhir ini. Didapatkan hubungan erat antara kebiasaan merokok, terutama sigaret, dengan timbulnya kanker paru paru. Bahkan ada yang secara tegas menyatakan bahwa rokok sebagai penyebab utama terjadinya kanker paru paru. Partikel asap rokok, seperti benzopiren, dibenzopiren, dan uretan, dikenal sebagai bahan karsinogen. Juga tar berhubungan dengan risiko terjadinya kanker. Dibandingkan dengan bukan perokok, kemungkinan timbul kanker paru paru pada perokok mencapai 10 30 kali lebih sering. Banyak penelitian telah membuktikan adanya hubungan merokok dengan penyakit jantung koroner PJK. Dari 11 juta kematian per tahun di negara industri maju, WHO melaporkan lebih dari setengah 6 juta disebabkan gangguan sirkulasi darah, di mana 2,5 juta adalah penyakit jantung koroner dan 1,5 juta adalah stroke. Survei Depkes RI tahun 1986 dan 1992, mendapatkan peningkatan kematian akibat penyakit jantung dari 9,7 persen peringkat ketiga menjadi 16 persen peringkat pertama. Merokok menjadi faktor utama penyebab penyakit pembuluh darah jantung tersebut. Bukan hanya menyebabkan penyakit jantung koroner, merokok juga berakibat buruk bagi pembuluh darah otak dan perifer. Asap yang diembuskan para perokok dapat dibagi atas asap utama main stream smoke dan asap samping side stream smoke. Asap utama merupakan asap tembakau yang dihirup langsung oleh perokok, sedangkan asap samping merupakan asap tembakau yang disebarkan ke udara bebas, yang akan dihirup oleh orang lain atau perokok pasif. Telah ditemukan 4. 000 jenis bahan kimia dalam rokok, dengan 40 jenis di antaranya bersifat karsinogenik dapat menyebabkan kanker, di mana bahan racun ini lebih banyak didapatkan pada asap samping, misalnya karbon monoksida CO 5 kali lipat lebih banyak ditemukan pada asap samping daripada asap utama, benzopiren 3 kali, dan amoniak 50 kali. Bahan bahan ini dapat bertahan sampai beberapa jam lamanya dalam ruang setelah rokok berhenti. Umumnya fokus penelitian ditujukan pada peranan nikotin dan CO. Kedua bahan ini, selain meningkatkan kebutuhan oksigen, juga mengganggu suplai oksigen ke otot jantung miokard sehingga merugikan kerja miokard. Nikotin mengganggu sistem saraf simpatis dengan akibat meningkatnya kebutuhan oksigen miokard. Selain menyebabkan ketagihan merokok, nikotin juga merangsang pelepasan adrenalin, meningkatkan frekuensi denyut jantung, tekanan darah, kebutuhan oksigen jantung, serta menyebabkan gangguan irama jantung. Nikotin juga mengganggu kerja saraf, otak, dan banyak bagian tubuh lainnya. Nikotin mengaktifkan trombosit dengan akibat timbulnya adhesi trombosit penggumpalan ke dinding pembuluh darah. Karbon monoksida menimbulkan desaturasi hemoglobin, menurunkan langsung persediaan oksigen untuk jaringan seluruh tubuh termasuk miokard. CO menggantikan tempat oksigen di hemoglobin, mengganggu pelepasan oksigen, dan mempercepat aterosklerosis pengapuran/penebalan dinding pembuluh darah. Dengan demikian, CO menurunkan kapasitas latihan fisik, meningkatkan viskositas darah, sehingga mempermudah penggumpalan darah. Nikotin, CO, dan bahan bahan lain dalam asap rokok terbukti merusak endotel dinding dalam pembuluh darah, dan mempermudah timbulnya penggumpalan darah. Di samping itu, asap rokok mempengaruhi profil lemak. Dibandingkan dengan bukan perokok, kadar kolesterol total, kolesterol LDL, dan trigliserida darah perokok lebih tinggi, sedangkan kolesterol HDL lebih rendah. Risiko terjadinya penyakit jantung koroner meningkat 2 4 kali pada perokok dibandingkan dengan bukan perokok. Risiko ini meningkat dengan bertambahnya usia dan jumlah rokok yang diisap. Penelitian menunjukkan bahwa faktor risiko merokok bekerja sinergis dengan faktor faktor lain, seperti hipertensi, kadar lemak atau gula darah yang tinggi, terhadap tercetusnya PJK. Perlu diketahui bahwa risiko kematian akibat penyakit jantung koroner berkurang dengan 50 persen pada tahun pertama sesudah rokok dihentikan. Akibat penggumpalan trombosis dan pengapuran aterosklerosis dinding pembuluh darah, merokok jelas akan merusak pembuluh darah perifer. PPDP yang melibatkan pembuluh darah arteri dan vena di tungkai bawah atau tangan sering ditemukan pada dewasa muda perokok berat, sering akan berakhir dengan amputasi.
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